\r\n\tWith the discovery of more unconventional heavier crude and alternative hydrocarbon sources, primary upgrading or cracking of the oil into lighter liquid fuel is critical. With increasing concern for environmental sustainability, the regulations on fuel specifications are becoming more stringent. Processing and treating crude oil into a cleaner oil with better quality is equally important. Hence, there has been a relentless and continuous effort to develop new crude upgrading and treating technologies, such as various catalytic systems for more economical and better system performance, as well as cleaner and higher-quality oil.
\r\n
\r\n\tThis edited book aims to provide the reader with an overview of the state-of-the-art technologies of crude oil downstream processing which include the primary and secondary upgrading or treating processes covering desulfurization, denitrogenation, demetallation, and evidence-based developments in this area.
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1. Introduction
Unsupervised machine learning has led to a wealth of clustering methods over the past few decades [1]. One of the important early ideas is that of the Parzen window distribution [2]. It has been introduced in 1962, as a kernel density estimate of a distribution function underlying measured data, and still serves as the basis of clustering algorithms in pattern recognition [1, 3]. Recently, it has been discovered [4] that the Parzen probability function can be decomposed into two components, weight and shape, which represent different aspects of the data. Weight, as its name implies, describes the semi-global strength of the distribution, whereas shape represents local properties which come to light once the bias of the weight is being removed. Moreover, −log(shape) coincides with a potential function V, which has been previously introduced in quantum clustering (QC) [5]. The cluster centers in QC correspond to minima of V. An alternative method, mean shift [6, 7], views the maxima of the probability function as the appropriate candidates of cluster centers. These two different points of view can now be studied and compared within a unified formalism [4].
Here we discuss the novel connections of the Parzen distribution to its potential and show how both can be used for the analysis of data points, leading to alternative clustering possibilities and extracting interesting features from the data. A particularly interesting set of applications appears in image analysis. Scale-space image analysis [8] has developed from the Parzen kernel methodology discussed in [6]. Now it turns out that insights from the potential term, or the shape component, allow for novel applications which are relevant to medical and technical imaging.
2. The Parzen probability distribution and its potential function
Data analysis often involves dimensionality reduction and noise removal, as well as some other tools, which eventually lead to consider a set of preprocessed data points located in a d-dimensional Euclidean space xi∈Rd, with possible positive attributes (e.g., intensities) Ii. For this set, we define the non-normalized Parzen window function with Gaussian kernels as
ψσx=∑iIie−x−xi22σ2E1
Following [4], we introduce a relative probability weight function representing the influence of the kernel at data point xi on any arbitrary point x:
pix=e−x−xi22σ2ψxE2
It obeys ∑iIipix=1 and allows for the definition of two new scalar functions over data space x, which are the potential and entropy fields
Vx=∑iIix−xi22σ2pixE3
Hx=−∑iIipixlogpixE4
Their difference is related to the Parzen probability function
Vx=Hx−logψxE5
This can be rewritten as
ψx=WxSxE6
using [4] the concepts of weight and shape: Wx=eHx and Sx=e−Vx.
Since Vx≥0, it follows that Sx≤1. Moreover, both W and S are nonnegative. S is integrable over x and, as such, can also serve as a distribution. From the definitions of (1) and (3), one can derive [4] the Schrödinger equation
−σ22∇2ψx+Vxψx=d2ψx,E7
which has been the cornerstone of the QC algorithm [5].
3. Interplay of scale and data space dependence
All the scalar fields over data space, introduced in the previous section, depend on the parameter σ, the scale of all Gaussian kernels. This dependence leads to further interesting relations between the Parzen probability function and its potential. Thus, from the definitions (1) and (3), it follows that
σ2∂∂σlogψσx=VσxE8
where we keep the index σ which has been suppressed in the previous section. This relation displays a direct connection between the two scalar functions defining the probability and the potential. We proceed now to introduce a vector field Dσ which is defined by
−∇logψσx=DσE9
and vanishes when the probability reaches its extrema in data space. Interestingly it is also related to the gradient of the potential function, through
−σ2∂∂σDσ=∇VσE10
Hence we conclude that the potential reaches its extrema when Dσ remains stationary with respect to variations of σ.
Its square U=D2 serves as an indicator function whose stationarity
σ2∂∂σUσx=2∇logψσx·∇Vσx=0E12
implies the existence of extrema of either the probability or the potential. Since U=D2 is nonnegative, U = 0 is a minimum in σ. It corresponds to extrema of ψ which are associated with D=0. Other values of U which obey Eq. (12) are associated with extrema of V which occur whenever ∂∂σDσ=0.Eq. (12) may be viewed as a statement concerning a set of points of interest in the data: all extrema of either the probability or the potential. In analogy with statistics, one may also view this equation as an inference method finding the parameter σ which leads to points of interest at given values of x.
Although all extrema may be regarded as points of interest, some are of more interest than others: extrema that remain fixed in x for a range of scale values, which is large compared with the range of scales of other points of interest. This criterion, introduced by Roberts [9], allows searching for scales which correspond to natural properties of the data. Thus it subserves the search for good clustering of the data [4, 5, 9].
Finally, we wish to point out that ψ is not a properly normalized distribution function. A proper probability function, whose integral is 1, is defined by
P=1N12πσ2d2ψxE13
where N=∑iIi. We note that ψ and V obey a joint integration constraint [10]
1N12πσ2d2∫dxψxVx=d2.E14
This may be interpreted as a constraint on the expectation value of the potential function in data space.
Examples of the behavior of logψ and of V are demonstrated in Figure 1 for a data set of 9000 observed galaxies (with redshift in the domain 0.47 ±0.005) regarded as points in spherical angles θ and φ within some limited range. Whereas for σ=2(in units of angle degrees), the two fields exhibit many extrema; there exist clear differences for larger sigma, for example, σ = 10, where logψ has one maximum, while V displays several minima. This figure is taken from [10], a paper which contains a detailed and expanded formulation of the analysis presented in this section.
Figure 1.
(a) Loci of 9000 Galaxies, downloaded from the Sloan Digital Sky Server DR12, within some limited range of spherical angles. Reproduced from [10]. (b) logψ (top) and V (bottom) displayed over the data plane 1a, using σ = 2 in spherical angle units. Reproduced from [10]. (c) Surfaces of V and logψ for increased values of the Gaussian width. Reproduced from [10].
4. Applications to clustering, image analysis, and more
4.1 Anomalies
Figure 1 serves as an example of different behaviors of logψ and of V. We wish to stress that when studying this system with large σ, the probability distribution is smooth; nonetheless underlying structure is observed in V. This means that, for a given σ, representing the large-scale behavior with one Gaussian, as one may be tempted to do after seeing the probability distribution, is wrong as demonstrated by the structures observed in V. On the other hand, the probability function tends to a smooth limit for σ = 10, whereas the fluctuating V changes with σ; hence V may represent random fluctuations in the data. However, comparing with the raw data in Figure 1a, we can be convinced that structure of the type discovered by V exists in the data. If these are fluctuations or not, one cannot tell from a single set of data.
A generally important question is if, within changing patterns of V, there exists one (or some) which remains relatively stable as function of σ. Such a structure may be viewed as a possible anomaly in the data. It is therefore advisable to study V when looking for anomalies.
4.2 Clustering
Clustering methodologies based on maximization of the probability and minimization of the potential can be defined by letting replica of data points move in these directions. These methods are known as mean shift (MS) and quantum clustering (QC) correspondingly. A recent review of MS techniques has been presented in [11]. Analyzing the same data with the same width-parameter σ leads to different clustering results for these two different methods, as is expected from Figure 1.
For illustration of clustering based on these different methods, we consider the crab data set which is included in Ripley’s textbook [12]. It consists of 200 instances belonging to four equally sized classes and is defined in a five-dimensional parameter space. Performing PCA and restricting ourselves to the 2D plane defined by PC2-PC3 lead to a challenging clustering problem which has been discussed by [13], when introducing support vector clustering (SVC), and by [5] when introducing QC. It has been used in other papers employing variations of QC, such as the recent study [14]. Here we will show the results of [4] who applied to these data three clustering methods: Maximal Shape Clustering (MSC) which coincides with QC, Maximal Probability Clustering (MPC) which coincides with MS, and Maximal Entropy Clustering (MEC). The quality of all three methods may be judged by applying the Jaccard score
J=n11n11+n10+n01
where n11 is the number of pairs of points which belong together both in the same class (accepted as “ground truth”) and in the same cluster, while n10 + n01 are numbers of pairs which belong to the same class but different clusters and vice versa. This test is performed in Figure 2a, demonstrating that QC wins the competition for a wide range of σ values. The expected asymptotic value is J = 98/398, befitting one cluster and four classes.
Figure 2.
(a) The Jaccard score, comparing clustering results with expert classification, comparing three clustering methods over a range of σ values. (b) The number of clusters, for each method and value of σ. Reproduced from [4]. MSC, MWC, and MPC stand for maximal shape, weight, and probability clustering accordingly. MSC coincides with quantum clustering and MPC with mean shift.
Another comparison is being made in Figure 2b. This follows Roberts’ criterion [9] that the preferable clustering method is the one which displays the most stable number of clusters with respect to variation of σ. This criterion is handy when the ground truth is unknown. QC excels also in this test, leading to a stable prediction of four clusters for a wide range of σ. This last figure also serve as a credibility test for Roberts’ criterion.
In order to make the clustering results more intuitive, we display in Figure 3, also taken from [4], topographic maps of the different fields describing probability, weight, and shape, for σ = 0.7. The points in four different colors represent the four different classes. The topographic maps allow one to understand the clustering results which represent the outcome of gradient ascent applied to replica of data points which climb toward their nearest peak. Comparing the topologies of Figure 3 with the results for σ = 0.7 in Figure 2 leads to an understanding of why the three methods differ from each other.
Figure 3.
Topographic maps of probability, weight, and shape, for σ = 0.7. Reproduced from [4].
4.3 Image analysis
A gray-scale image may be analyzed as a set of inputs associated with different pixels. In higher dimensional problems, such as 3D MRI data, the pixels are replaced by voxels. Both may fit well into our analysis which starts with Eq. (1), associating a probability distribution with every image. One may then wonder if the weight-shape decomposition of Eq. (6)
ψx=WxSx
can lead to any novel understanding of image analysis.
In any practical application, non-normalized probability and weight may have very large amplitudes, yet shape will be limited to values ≤1. Nonetheless it carries some important characteristics:
Shape may be normalized to become a distribution on its own.
Shape serves as a generalized edge detector.
Shape is the basis of QC; hence the latter is very relevant to clustering of regions where shape is large. Alternative methods may be relevant when shape is small.
The first claim is trivial since S is limited to the range 0≤S≤1, and the Gaussian kernels are integrable. The second property is a result of Eq. (7) which shows that the potential is related to the second derivative of the probability. It has led to an interesting result in [4], demonstrating that line caricatures of images can be produced by thresholded shape drawings.
To demonstrate the third point, we display in Figure 4 the results of an analysis of a T2 MRI of the brain of a Macaque monkey [15]. Following the general procedure outlined above, and limiting ourselves to large relative values (thresholded distributions) of probability and shape, we find that the latter peaks in cortical regions, whereas the former peaks in internal regions of the brain, as demonstrated in Figure 4. Thus, a simple thresholding procedure allows one to easily segment the MR image, for the purpose of further analysis of the cortex by applying QC to the data in the large S domain. In Figure 5, we follow these conclusions [15] with a display of QC clusters projected onto the surface of the brain, leading to its parcellation into cortical components which are derived by just computational image analysis.
Figure 4.
Thresholded shape (red) and thresholded probability (blue) dominate different regions within the same MR image of a macaque brain, projected on its y-z plane. This analysis used σ = 3 in voxel units. Data outside the brain are due to artifacts and noise in the MR image. These results are due to [15], and they indicate that large shape components dominate cortical regions of the T2 MRI brain image.
Figure 5.
Characteristic results of QC cortical clusters as mapped onto the surface of the brain and projected onto the x-y plane. This figure displays a map of the largest clusters of shape, each described by a different color. These results are due to Fisher [15].
4.4 Convolutional representation of V
When one analyzes data in a regular underlying structure, such as pixels m of an image I(m), the translational invariance of the Gaussian kernel allows one to use a convolutional description such as
ψm=∑nInKm−n=I∗KmE15
with K being a discrete representation of the kernel. This leads [4] to the following result for the potential
Vm=I∗LmI∗KmE16
where L = −K log K. Such 3D kernels were applied to brain MR images [15] leading to the results displayed in Figures 4 and 5.
Noting that Eq. (15) is reminiscent of a convolutional layer in a deep network [16], we hypothesize that it can be useful to incorporate intermediate layers with nonlinear filters such as Eq. (16), as additional non-trained pooling filters in deep networks.
4.5 Computational remarks
The clustering methodology which has been employed in the different examples shown above is the simplest flavor of gradient descent (or ascent). It calculates the relevant fields on the basis of the data points and continues with straightforward dynamics that have been applied to replica of data points, seeking the extrema of the fields. Various alternatives to this basic application exist. The most important one is hierarchical clustering, which allows for conceptual simplicity and saves computational complexity. Such methodologies were described and discussed in [11] and in [4].
Computational complexity is an obvious issue when working with large data sets. Thus, 3D MRI data may easily comprise 1 M points, whereas their manipulation within a system like MATLAB may well be limited to handling only 40 K points at a time [15]. One way to overcome such issues is to consider performing the analysis within extended voxels, for example, voxels containing three pixels in each direction in a 3D image problem. Within each new voxel, one may simply sum the intensity of points, leading to a new presentation of the data in the form of Eq. 1 on the smaller extended voxel space. Clearly one has to make sure that such an approximation does not harm interesting features of the data.
When analyzing other big data, no prior dimensional representation may be required. For the sake of noise reduction and computational complexity, it is advantageous to first apply relevant dimensional reduction, as provided, for example, by singular value decomposition (SVD) and principal component analysis (PCA). It is also important to make sure that the different axes are of similar scale, as shown in the example of Figure 3. When the data is still large, one may apply the trick of extended voxels described above. For very large data, one may also separate the data into several components, as is customary in supervised learning, to make sure that conclusions are not affected by the random choice of a subset of the data.
5. Conclusions
In the past (see, e.g., [3]), Parzen analysis has not considered the potential field V, which plays an important part in the understanding of different features of the data. In particular, V is sensitive to small changes in the Parzen probability by being related to its second derivative. It is also the basis of quantum clustering whose advantages have been demonstrated here as well as in many other investigations in the literature. The discovery of the weight-shape decomposition of the Parzen probability has led to a focus on shape and on the potential and allows for a meaningful comparative discussion of the different features which may be extracted from data.
Here we have defined a set of fields in data space which hopefully will turn out to serve as useful tools in future data analyses. They seem to be adequately applicable to image analysis, and we expect them to be particularly useful in biomedical and technical image analyses in three dimensions. When analyzing other data, where no visual display constraints exist, noise reduction and computational complexity call for preprocessing by dimensional reduction. Further reduction of computational complexity may be tried by employing extended voxels, which our technique can easily accommodate.
In summary, this extended Parzen method replaces any set of discreet data by a continuous set of fields in data space, with interrelations in scale space. It allows for investigating data properties in terms of these fields and their extrema.
Acknowledgments
This work has been partially supported by the Blavatnik Cyber Center of Tel Aviv University. I thank Itay Fisher for his help with numerical data analysis.
Conflict of interest
The author declares no conflict of interest.
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This probability function can be decomposed into the product of two components, weight (W) and shape (S), which represent different aspects of the data. We demonstrate how this naturally leads to a formalism of fields in data space, which are interconnected through relations in one-dimensional scale space, corresponding to the common Gaussian width. We discuss the connection of this formalism to different clustering procedures such as quantum clustering (QC) and mean shift (MS). We demonstrate on various examples the importance of these concepts in the analysis of natural data as well as in image analysis in two or three dimensions.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65444",risUrl:"/chapter/ris/65444",book:{id:"7405",slug:"pattern-recognition-selected-methods-and-applications"},signatures:"David Horn",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The Parzen probability distribution and its potential function",level:"1"},{id:"sec_3",title:"3. Interplay of scale and data space dependence",level:"1"},{id:"sec_4",title:"4. Applications to clustering, image analysis, and more",level:"1"},{id:"sec_4_2",title:"4.1 Anomalies",level:"2"},{id:"sec_5_2",title:"4.2 Clustering",level:"2"},{id:"sec_6_2",title:"4.3 Image analysis",level:"2"},{id:"sec_7_2",title:"4.4 Convolutional representation of V",level:"2"},{id:"sec_8_2",title:"4.5 Computational remarks",level:"2"},{id:"sec_10",title:"5. Conclusions",level:"1"},{id:"sec_11",title:"Acknowledgments",level:"1"},{id:"sec_14",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Xu D, Tian Y. A comprehensive survey of clustering algorithms. Annals of Data Science. 2015;2(2):165-193'},{id:"B2",body:'Parzen E. On estimation of a probability density function and mode. The Annals of Mathematical Statistics. 1962;33(3):1065-1076'},{id:"B3",body:'Duda RO, Hart PE, Stork DG. Pattern Classification. 2nd ed. New York: Wiley-Interscience; 2001'},{id:"B4",body:'Deutsch L, Horn D. The weight-shape decomposition of density estimates: A framework for clustering and image analysis algorithms. Pattern Recognition. 2018;81:190-199'},{id:"B5",body:'Horn D, Gottlieb A. Algorithm for data clustering in pattern recognition problems based on quantum mechanics. Physical Review Letters. 2001;88(1):018702'},{id:"B6",body:'Cheng Y. Mean shift, mode seeking, and clustering. IEEE Transactions on Pattern Analysis and Machine Intelligence. 1995;17(8):790-799'},{id:"B7",body:'Comaniciu D, Meer P. Mean shift: A robust approach toward feature space analysis. IEEE Transactions on Pattern Analysis and Machine Intelligence. 2002;24(5):603-619'},{id:"B8",body:'Lindeberg T. Scale-space theory: A basic tool for analyzing structures at different scales. Journal of Applied Statistics. 1994;21(1–2):225-270'},{id:"B9",body:'Roberts SJ. Parametric and non-parametric unsupervised cluster analysis. Pattern Recognition. 1997;30(2):261-272'},{id:"B10",body:'Horn D. Field Formulation of Parzen Data Analysis. arXiv eprint 1808.08776. 2018'},{id:"B11",body:'Carreira-Perpiñán MA. Clustering methods based on kernel density estimators: Mean-shift algorithms. In: Hennig C, Meila M, Murtagh F, Rocci R, editors. Invited chapter in Handbook of Cluster Analysis. Chapter 18. UK: CRC/Chapman and Hall (Taylor & Francis Group); 2015. pp. 383-418'},{id:"B12",body:'Ripley BD. Pattern Recognition and Neural Networks. Cambridge, UK: Cambridge University Press; 1996'},{id:"B13",body:'Ben-Hur A, Horn D, Siegelmann HT, Vapnik V. Support vector clustering. Journal of Machine Learning Research. 2001;2(Dec):125-137'},{id:"B14",body:'Scott TC, Therani M, Wang XM. Data clustering with quantum mechanics. Mathematics. 2017;5:5. DOI: 10.3390/math5010005'},{id:"B15",body:'Fisher I. Parcellation of brain images using shape analysis [M.Sc. thesis]. Tel-Aviv University; 2018. http://horn.tau.ac.il/publications/FisherThesis.pdf'},{id:"B16",body:'LeCun Y, Bengio Y, Hinton G. Deep learning. Nature. 2015;521:436-444'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"David Horn",address:"horn@tau.ac.il",affiliation:'
Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, Israel
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Pathotypes",doi:"10.5772/intechopen.101567",slug:"the-biology-and-the-evolutionary-dynamics-of-diarrheagenic-escherichia-coli-pathotypes",body:'
1. Introduction
Escherichia coli inhabits and adapts to different hosts, a quest that resulted in the acquisition and loss of genes, which further drive diversity in this bacterium and contribute to the evolution of harmless strains to pathogenic lifestyles [1]. While E. coli is an integral part of the microbiota of different hosts, it can also cause severe infections in humans and animals [2, 3]. A subgroup of E. coli that are pathogenic can cause a broad range of human diseases due to evolution that resulted in the development of patho-features enabling it to adapt and survive in different environments. These environments range from the gastrointestinal tract to extraintestinal sites such as the urinary tract, or meninges, [4] in addition to fecal contamination of food that could cause enteric infection resulting from food poisoning or contamination [5]. Based on the type of infection they cause, pathogenic E. coli are divided into intestinal or diarrheagenic E. coli (DEC) that cause diarrheal illness and extraintestinal E. coli (ExPEC) that are implicated in infections such as urinary tract infections [3]. Diarrheal illness constitutes a public health burden and is a leading cause of mortality worldwide, causing >300 million illnesses and about 200,000 deaths annually, particularly in children in developing countries, including sub-Saharan and Southeast Asian countries (Figure 1) [6, 7].
Figure 1.
Global mortality rate from diarrhea in children under 5 years in 2016. Data represent the analysis of diarrhea burden in 195 countries in 1990–2016, showing the regions most affected by the illness. Reprinted from Troeger et al. [6] which was published under Creative Commons License.
The treatment of E. coli associated illness is toppled by its growing resistance to antibiotics, culminated by either the acquisition of resistance determinants or mutations that encodes for low uptake and tolerance to a higher concentration of the antimicrobials. Hence, E. coli could serve as a major reservoir of resistance genes not only for other E. coli strains but also for Enterobacteriaceae [8]. In addition, virulence determinants and genes that are associated with stringent response in nutrient low environments could also be acquired, thereby contributing to the survival and persistence of this bacterium in its environment [9]. Transmission of these antibiotic-resistant or pathogenic E. coli strains between different hosts, particularly in animals and humans could be through several routes such as direct contact with fecal-contaminated samples or other secretions from animals, or via the consumption of contaminated food [5].
Assessing the antimicrobial resistance, virulence, and transmission dynamics of E. coli requires characterization of this bacterium. A widely accepted classic method for characterizing E. coli is the serotyping technique that is based on the Kauffman classification scheme, where the O (somatic) polysaccharides and H (flagellar) surface antigens are determined [10, 11]. Other methods of typing and assessing the genetic relatedness and detecting outbreaks of E. coli strains are pulsed-field gel electrophoresis (PFGE) [12], multilocus enzyme electrophoresis (MLEE) [13], multilocus variable-number tandem repeat analysis (MVLA) [14], or multilocus sequence typing (MLST) [15]. These methods have proven to be effective in the epidemiological investigation of pathogenic E. coli [16] and the assessment of the emergence and dissemination of multidrug-resistant clones. However, none of these methods can accurately define the evolutionary relationships between E. coli strains, hence the need for a tool with a higher resolution. The advent of whole-genome sequencing (WGS) technologies has greatly enhanced not only the epidemiological investigation of outbreaks and the global spread of multidrug resistant and pathogenic clones of E. coli [17], but also our understanding of the physiology and evolutionary history of how some pathogenic strains evolve from commensal E.coli strains.
Based on clinical manifestation, presence of specific virulence determinants and phylogenetic profiles, diarrheagenic E. coli are categorized into six main pathotypes namely, enterotoxigenic E. coli (ETEC), enterohaemorrhagic E. coli (EHEC) or Shiga toxin-producing E. coli (STEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), entero-invasive E. coli (EIEC), and diffusely adherent E. coli (DAEC) [3, 7]. This chapter provides a snapshot of the biology of E. coli by focusing on the resistome, virulome, as well as the population structure of diarrheagenic E. coli pathotypes.
2. Enterotoxigenic E. coli (ETEC)
2.1 An overview of ETEC
Enterotoxigenic E. coli (ETEC) is a major cause of travelers’ diarrhea, with a high prevalence in developing countries and responsible for about 200 million cases of diarrheal illnesses and 100,000 deaths each year [18, 19]. The incidence of ETEC could be recovered from symptomatic and asymptomatic carriers and is most common in younger children with a high mortality rate in this group. In regions such as Africa, South America, and Southeast Asia the incidence of ETEC-related infection is estimated to be at least one to two episodes per year [3] further reinforcing the significance of this pathotype in that region. While ETEC is not limited to humans, it is also a common cause of edema and post-weaning diarrheal diseases in food production animals such as cattle, pigs, and sheep [20]. ETEC are transmitted through the fecal-oral route by contaminated food as well as surface and groundwater in developing countries with limited access to clean water (Figure 2) [3, 6].
Figure 2.
Dissemination and transmission routes of pathogenic Escherichia coli pathotypes. Solid black arrows represent a direct transmission while gray arrows depict an indirect transmission of pathogenic E. coli pathotypes. ETEC: Enterotoxigenic E. coli; STEC: Shiga toxin-producing E. coli; EPEC: Enteropathogenic E. coli; EAEC: Enteroaggregative E. coli; EIEC: Entero-invasive E. coli; DAEC: Diffusely adherent E. coli.
There is a great genetic diversity in ETEC as more than 100 different O antigens have been reported to be associated with clinical isolates. Among these, the O6 serogroup is most common, and geographically diverse among all ETEC serogroups, and has been implicated in multiple outbreaks in different countries [21]. Additionally, at least 34 H antigens are also associated with this pathotype. Among the serotypes as determined by the combination of O and H antigens, O6:H16 (heat-stable (ST) or heat-labile (LT) toxin), O148:H28 (ST), O167:H5, O153:H45 (ST), O169: H41 (ST only) are frequently isolated from humans, animals, environmental matrices, and from outbreaks in developing countries [22, 23, 24]. ETEC produces one or more colonization factors that facilitate its attachment to specific receptors on the mucosal layer of the small intestine of humans and animals, and secretes enterotoxins that cause electrolyte imbalance in the intestinal lumen resulting in dehydration, metabolic acidosis, and diarrheal [3, 18]. The ST toxin is a nonimmunogenic small protein molecule, but the LT toxin is structurally homologous and exhibits a similar mechanism of action to cholera toxin produced by Vibrio cholerae [23, 25].
2.2 Virulome of ETEC
ETEC employs an array of genetic factors that are either chromosomal or plasmid-borne that mediate colonization and adherence to the intestinal epithelium, proliferation within the host, and evasion of host defense mechanisms (Table 1) [26].
E. coli pathotypes
Main reservoir
Clinical presentations
Virulence factors
ETEC
Humans and animals
Watery noninflammatory diarrhea, adherence to small intestinal epithelium, nutrient malabsorption
Summary of the clinical characteristics and virulence factors of Escherichia coli pathotypes.
Legend: ETEC: Enterotoxigenic E. coli; STEC: Shiga toxin-producing E. coli; EPEC: Enteropathogenic E. coli; EAEC: Enteroaggregative E. coli; EIEC: Entero-invasive E. coli; DAEC: Diffusely adherent E. coli.
2.2.1 Colonization and adhesion
Colonization and adhesion are the primary and essential steps in the pathogenesis of pathogens. ETEC is not an exception as the colonization of the host intestinal epithelium by this pathotype is mediated by plasmid-borne genes that encode adhesins and one or more colonization factors (CFs) namely, pilus or pilus-related adhesins [23]. Pili are hair-like appendages on the cell surface of bacteria where they mediate the attachment of bacteria to surfaces.
They are composed of protein subunits (pilins) that are structurally polymeric and are almost exclusively plasmid-borne (Figure 3) [27]. ETEC CFs are designated as CS (coli surface antigens) followed by a number, except for CFA/I and PCFO71 [27]. Presently, at least 30 CFs have been reported in ETEC of human origin. It is estimated that about 50% of strains in this pathotype carry one or more CFs that are not detectable, suggesting that there could be more CFs that are yet to be discovered and characterized [18, 23]. The co-expression of one or more CFs with toxin-encoding genes has been described. For example, CFA/I + LT, CS7 with LT, CS5 + CS6 with LT + ST, CS2 + CS3 with LT + STh, among others [28, 29]. In the prototypical ETEC strain H10407, the production of CFA/I is mediated by cfaABCE operon that is tightly regulated by CfaD, a transcriptional regulator that triggers its expression.
Figure 3.
Colonization and adherence patterns of diarrheagenic Escherichia coli to the host epithelium. Enterotoxigenic E. coli (ETEC) uses colonization factors (CFs) to attach to host intestinal mucosa. Shiga toxin-producing E. coli (STEC) and Enteropathogenic E. coli (EPEC) attach to the intestinal epithelial cells and efface microvilli, forming characteristic A/E lesions. EPEC also forms microcolonies using bundle-forming pili (Bfp) resulting in a localized adherence pattern. Enteroaggregative E. coli (EAEC) forms a biofilm matrix on the intestinal mucosa that promotes the formation of a “stacked brick” adherence pattern. Enteroinvasive E. coli (EIEC)/Shigella are intracellular pathogens that penetrate the intestinal epithelium through M cells to gain access to the submucosa. Diffusely adherent E. coli (DAEC) is scattered over the surfaces of intestinal cells, resulting in a diffuse adherence pattern.
Other plasmid-encoded genetic factors that have been reported to play a significant role in the pathogenesis of ETEC include a class I SPATE (serine protease autotransporters of the Enterobacteriaceae) EatA that digests EtpA secreted by ETEC, thereby promoting the adhesion of flagella to the host receptor [30, 31]. ETEC can invade the host cell with two chromosomally encoded genes tia and tibA. The former (tia gene) is borne on a 46-kb pathogenicity island (PAI). The expression of these genes was reported to be associated with adhesion and invasion of ETEC in host cells [27]. Likewise, a leoA gene encoding GTPase is reported to be associated with virulence in ETEC (Table 1) [32].
2.2.2 Enterotoxin secretion
One of the salient features that define ETEC is its ability to produce two types of enterotoxins, ST or LT [23]. STs are non-antigenic small enterotoxins that are frequent in human diseases, found in about 80% of ETEC either singly or in combination with LT [18, 33]. STs are classified into two different classes (STa and STb) based on their structure and function. STa is soluble in methanol and protease-resistant. It is frequent in human diseases and encoded by estA genes, whereas STb is insoluble in methanol and sensitive to protease, and causes disease only in animals and is encoded by estB gene [34]. Based on host specificity, STa is further designated into two genetic variants namely STp and STh. The former (STp) is 18 amino acids in length and produced by ETEC strains of porcine, bovine, and human origin, while STh is 19 amino acids long and exclusive in ETEC strains of human origin [29]. Recently, six genetic variants of STa encoding gene (estA) have been reported, where estA1, estA5, and estA6 are common in ETEC strains of porcine origin and estA2, estA3/4 and estA7 are frequent in isolates of human origin (STh), while estA5 gene is described to be frequent in ETEC strains causing disease both in animals and humans, especially traveler’s diarrhea in adults [29, 34]. Secretion of STh and STp in the intestinal epithelium of the host requires the efflux protein TolC [35].
Unlike, STs, LTs are hexameric and strongly immunogenic that are encoded by the eltAB operon [29]. LTs have two subtypes: LT-I and LT-II, both of which have been reported in ETEC strains causing diarrhea in humans and in different species of post-weaned animals. LT-Is are plasmid-borne and highly similar to cholera toxin produced by V. cholera [3, 36]. Conversely, LT-II is chromosomal and has been hypothesized to be prophage encoded [3, 36]. LT-II is classified into LT-IIa, LT-II, and LT-IIc, with LT-IIc being the more frequent in LT-II ETEC strains [36].
LTs promote the adherence of ETEC to host intestinal epithelial cells and evade the host defense mechanisms by inhibiting the expression of antimicrobial peptides produced by the hosts, in addition to the activation of host signaling pathways [3]. Another virulence factor encoding enterotoxin in ETEC strains is enteroaggregative heat-stable toxin (EAST1). EAST1 toxin is heat-stable and 38 amino acids long encoded by astA gene that is commonly plasmid-borne [37]. ETEC strains producing EAST1 toxin have been recovered from humans and animals. This toxin was reported to have originated from EAEC but it is prevalent in ETEC [38, 39]. While the role of EAST1 toxin in enteric infection is not clear, there has been evidence and direct associational studies linking this toxin to diarrheal illness [38]. EAST1 toxin is functionally and structurally similar to STa, sharing 50% identity in their functional regions [38]. Overall, enterotoxins secreted by ETEC strains have a similar mechanism of causing diarrheal diseases in the host. ETEC enterotoxins increase cyclic AMP or cyclic GMP levels in the intestinal epithelium of the host. This results in excessive secretion of chloride and reduction in the adsorption of sodium chloride in the intestinal epithelium thereby resulting in electrolyte imbalance, fluid loss and dehydration [29, 40].
2.3 Antibiotic resistance in ETEC
Since the first isolation of ETEC in Kolkata about five decades ago [41], the emergence and increase in multidrug-resistant strains have been reported. A homogenous and high antibiotic susceptibility pattern was observed for ETEC strains at a time but the treatment of travelers’ diarrhea with different classes of antimicrobials such as macrolides (erythromycin and azithromycin), fluoroquinolones (norfloxacin, ofloxacin, ciprofloxacin), tetracycline (doxycycline), rifamycin and sulfamethoxazole-trimethoprim that are used to treat other types of infections [22] may have also contributed to the emergence of antimicrobial resistance in this pathotype [22]. Another contributor could be the indiscriminate use of antibiotics for the treatment of diarrheas caused by viral agents that are sometimes misdiagnosed because they present similar symptoms [3].
There are several studies from different countries assessing the antibiotic resistance profile and distribution of resistance determinants in ETEC. In a study, the antimicrobial resistance profile among patients with recent travel history to ETEC endemic regions between 2001 and 2004 reported that up to 60% of the ETEC isolates were resistant to sulfamethoxazole-trimethoprim, tetracycline, and/or ampicillin [42]. Ciprofloxacin resistance was reported to markedly increase from 1% to 8% within 10 years (1994–2004) in patients [42] which clearly suggests a rapid emergence of resistance with time in this pathotype. In a recent study on the WGS analyses of eight strains representing the major ETEC lineages that are causing diarrheal diseases in humans around the globe, all the strains showed resistance and carried resistance determinants to at least two of the 14 antibiotics tested, with resistance to penicillin, norfloxacin and chloramphenicol being the most common. In this study, two plasmids designated (pAvM_E1441_17 and pAvM_E2980_15) carried resistance determinants to mercury (mer operon) and multiple antibiotics including streptomycin (aadA1-like, strA, and strB) and ampicillin (blaTEM-1b, ampC) [43].
ETEC in animals, however, may be slightly different. In a study of 112 ETEC isolates recovered from pigs in Canada over a two-decade period (1978–2000), tetB gene that encodes resistance to tetracycline was the most common and found in 80% of the collection [44]. Another interesting observation from this study was the increase in the determinants encoding resistance to gentamicin (aac(3)-IV), kanamycin (aph(3′)-Ia) and trimethoprim (dhfrV), while others appear to be either consistent or decrease over time [44].
2.4 Population structure of ETEC
ETEC strains are epidemiologically and phenotypically diverse and exhibit high genetic diversity. In addition to being polyphyletic, the distribution of ETEC lineages is not restricted by geography [45]. Several reports on the phylogenetic analyses of strains from the human origin using MLEE and MLST, and well as CF-toxin-based phylogeny showed that this pathotype might have evolved multiple times through clonal expansion and probably due to lack of common clonal lineage [46, 47]. In spite of the genomic diversity among strains in this pathotype, Turner and colleagues [48] reported ETEC to be associated with sequence type 10 (ST10). In a broader evolutionary study of a large collection of 1019 ETEC isolates from humans in 13 countries using MLST, 42 clonal groups were observed with evidence for horizontal gene exchange of plasmid-encoded CF genes between the lineages [46]. Since the advent of next-generation sequencing technologies, the study of the population structure of ETEC has improved the understanding of the genetic diversity and evolution of the pathotype [24, 49, 50].
A global collection of ETEC isolates from humans collected over a period of three decades (1980–2011) in 20 countries and representing four continents was assessed for genetic relatedness using WGS-based single nucleotide polymorphism (SNP) [49]. Indeed, ETEC strains are genetically diverse as they were reported to be distributed across different E. coli phylogenetic groups (A, B1, B2, D, and E) (Figure 4), an observation that is also in accordance with the structure defined by MLST [46, 48, 51]. An interesting finding from the study that could be attributed to the higher resolution of WGS was the identification of ETEC-specific clusters (L1-L14) that clustered geographically diverse strains that were phylogenetic related and associated with specific plasmid-encoded virulence determinants. The L1 and L2 clustered the commonly found ETEC strains expressing O6 antigen and carried similar profiles for CF and LT and ST enterotoxins, suggesting that these plasmid-encoded virulence determinants could be important to understand the evolutionary histories of these clusters [24, 49].
Figure 4.
Single nucleotide polymorphism based Phylogenetic tree of Escherichia coli. Draft genomes of E. coli pathotypes were downloaded from NCBI and core genomes were defined and aligned against E. coli K12. SNPs from the core genome alignment were called using Snippy (https://github.com/tseemann/snippy). Concatenated SNPs alignment cured of recombination (https://github.com/sanger-pathogens/gubbins) was used to construct a phylogenetic tree and visualized using iTOL (http://itol.embl.de/). Different colors and shapes depict E. coli phylogroups and pathotypes, respectively.
Similarly, in a local study on the phylogenomic diversity of 94 ETEC isolates from Bangladesh [24], a polyphyletic scenario and a direct correlation between lineages and virulence profiles and CFs were noted. Using comparative genomic tools, the authors identified six novel CF variants. However, the experimental validation of these CFs would be important to decipher their association with other virulence determinants as well as their interaction with the host cells.
3. Shiga toxin-producing E. coli (STEC)
3.1 An overview of STEC
Shiga toxin-producing E. coli (STEC), also known as verocytotoxin-producing E. coli (VTEC) was first identified as a pathogen in 1982 and is defined by the presence of Shiga toxin genes (stx1 and stx2) that are known to be encoded on lambdoid prophages [52]. STEC had since emerged as a major enteric foodborne and zoonotic pathogen causing gastroenteritis and enterocolitis. STEC-related infection could progress to hemolytic-uremic syndrome (HUS) that in some cases could be fatal or result in renal failure in children (Table 1) [3]. Enterohemorrhagic E. coli (EHEC) is associated with hemorrhagic colitis which makes it a subset of STEC pathotype [3, 53]. STEC causes more than one million cases annually with about 30% of such cases found in the United States [54]. According to Blanco et al. [55], 435 STEC serotypes strains have been identified but only a few are frequently associated with human infection among which are O26, O45, O103, O111, O121, O145, and O157 [56, 57]. STEC O157:H7 has been widely studied most likely because it is frequently implicated in STEC foodborne outbreaks. Although a series of outbreaks that are mostly caused by STEC O157:H7 have been reported globally in developed and developing countries, some are believed to go undetected or underreported [54, 58].
The main reservoir for STEC strains causing infection in humans are known to be ruminant food production animals including cattle, sheep, and goats. These animals are asymptomatic carriers and shedders as the vascular receptor that facilitate the transportation of the Shiga toxins to organs are absent. This E. coli pathotype is also common in the gastrointestinal tracts of poultry, pigs as well as some companion animals such as dogs and cats [59]. Other STEC asymptomatic carriers have been reported in other ruminant and monogastric animals, as well as in insects, suggesting their roles in the food contamination, dissemination, and transmission of different strains of this pathotype to humans (Figure 2) [59, 60]. Since STEC is part of the intestinal flora of food-production animals and is readily shed through feces, direct contact with contaminated environmental matrices and/or the consumption of contaminated products including undercooked meat, unpasteurized dairy products, vegetables, and/or water are a potential route of transmission of different strains of this pathotype to humans [61, 62]. STEC transmission due to direct contact with infected person or animals or their environments or products has been documented [63].
3.2 Virulome of STEC
STEC carries genes encoding adhesins and enterotoxins that are either chromosomal, on PAIs, or plasmid-borne. These determinants mediate colonization, attachments, and invasion of host cells (Table 1) [64].
3.2.1 Colonization and adherence
Ingestion of contaminated food or direct contact with contaminated environmental matrices or infected persons or animals precedes STEC-related diseases. Colonization and attachment/adherence of STEC to intestinal epithelium is mediated by several genetic factors some of which are carried by the locus of enterocyte effacement (LEE) PAI [65]. LEE locus which is also often present in EPEC strains [66] encodes a type III secretion system (T3SS) that plays a role in the secretion and translocation of virulence-associated genetic factors into host cells [67]. One of these genetic factors is eae gene that encodes intimin, an adhesin that is essential for the attachment of STEC to the host intestinal mucous membrane and facilitates the production of attaching-and-effacing (A/E) lesion (Figure 3) [65]. The injection of its translocated intimin receptor (Tir) into the host cells and the interaction between this protein (Tir), proteins that form the needle component of the T3SS (EspADB), and intimin facilitates the induction of lesions [65, 68]. Intimin has at least 30 reported subtypes [69] and some of these variants are associated with specific serotypes. Oftentimes, intimin encoding gene (eae) subtype γ1 is associated with STEC O157:H7 and O145:H28 [69, 70], while subtypes β1, ε, and θ are frequently found in O26:H11, O103:H2 and O111:H8 STEC strains, respectively [69, 70]. Intimin is reported to be common in clinical strains of STEC with a prevalence that could range from 70 to 90% [71, 72, 73].
LEE is unarguably important for the pathogenesis of STEC strains, but STEC LEE-negative strains/serotypes (e.g. O103:H21) have been implicated in infections [74]. This implies that there are several other virulence-associated factors that are carried on PAIs or mobile genetic elements mediating colonization and adherence to host cells in these strains [74]. For example, a gene (saa) encoding autoagglutinating adhesin was isolated from a large plasmid of a LEE-negative STEC O113:H21 implicated in an outbreak. The expression of this gene is described to enhance adherence of STEC strains to HEp-2 cells [75]. Other protein-encoding genes reported to promote the colonization and adherence of STEC strains to mucosal membrane include paa that encodes attachment of bacterial cells to enterocytes in pigs [76], ehaA a STEC autotransporter [77], lpfA, long polar fimbriae [78] that are both involved in the attachment of STEC to surfaces. Additionally, “O” islands (OI) that encode macrophage toxin and ClpB-like chaperone (OI-7), urease clusters (OI-43 and OI-48), two toxins and PagC-like virulence factor (OI-122) among others have been reported to be linked with virulence in STEC [57, 79].
3.2.2 Cytotoxic toxin production
STEC-related infections in humans are reported to be associated with the presence and expression of several virulence determinants, with the phage-encoded Shiga toxin genes Stx1 (Stx1a) and Stx2 (Stx2a) being the main virulence factors [64, 80]. Stx1 consists of 293 amino acids while the Stx2a is longer by only four amino acids. At least, 16 subtypes of these two toxins have been described based on amino acid differences and the level of cytotoxicity. Stx1 contains four variants encoded by stx1a, stx1c, stx1d and stx1e, whereas Stx2 comprised 12 subtypes encoded by stx2a, stx2b, stx2c, stx2d, stx2e, stx2f, stx2g, stx2h, stx2i, stx2j, stx2k and stx2l [80]. While Stx1a has been implicated in human infection, Stx2a, Stx2c, and Stx2d are the major subtypes that are frequently associated with hemorrhagic colitis and HUS [64]. However, Stx2a and Stx2d subtypes are described to exhibit higher cytotoxicity relative to Stx2b and Stx2c in a mouse model [64, 81]. The interaction of Stxs with the host cell receptor is very complex and is based on characteristics of the environment of the receptor in the plasma membrane [64]. Stxs bind to the globotriaosylceramide Gb3, an insoluble molecule that has multiple binding sites and comprised a lipid component. The interaction between these two molecules (Stx and Gb3) is described to be important in the uptake of the toxin (Figure 3). Stxs are ribotoxins that disrupt protein synthesis within the host cell and provoke apoptosis [64, 81].
STEC strains can carry stx1 or stx2 genes or both [2]. In a study of 351 STEC strains from bovine feces, the great majority of the strains (82%) carried stx2 while 18% carried stx1. Both genes were found only in ~3% of the collection [2]. In another study involving 220 STEC strains from humans and animals, stx1 and stx2 were found in 15% and 53%, respectively, while both genes were found in 32% of the isolates [82]. Stxs subtypes are heterogeneously distributed in the population, but specific variants have been reported to be host-specific. For example, Stx2e is less cytotoxic and sporadic in human diseases, and is commonly associated with edema diseases in weaned pigs [83]. Likewise, Stx1c is reported to be associated with STEC of ovine origin [84]. Indeed, the severity of STEC infection has been noted to be directly proportional to a number of Stx types or subtypes carried by the infecting strains [85]. While the production of only Stxs has been described to cause HUS, the infection is however exacerbated when associated with other virulence determinants including the LEE [21]. In addition to Stx, other toxins or hemolysins have been reported to be associated with STEC virulence. These include the hemolysin, encoded by the ehxA or hlyA gene, that are usually found on megaplasmid pO113 and/or pO157 and linked to cytotoxic effects on endothelial cells that may also promote the development of HUS [86, 87]. Other virulence determinants carried on these plasmids include toxB that is essential for adherence of STEC to host cells [88], espP that encodes an extracellular protease and katP that is associated with catalase-peroxidase production important for oxidative stress response [89].
3.3 Antibiotic resistance in STEC
Treatment of STEC infections with antibiotics is not encouraged as this might exacerbate the disease by activating the lytic cycle of the phage carrying Shiga toxin that could aggravate tissue damage in infected individuals. Antibiotics such as rifaximin, fosfomycin, azithromycin, and meropenem that do not encourage the release of Shiga toxin have been used for the treatment of early onset of STEC infection to prevent the progression of the diseases to HUS [90].
Several studies on the prevalence of antibiotic resistance in STEC from different countries and host or environments have reported that resistance to beta-lactams, sulfonamide, tetracycline, and trimethoprim are common STEC, while multidrug-resistance is more frequent in non-O157 than O157:H7 serotypes [91]. For STEC O157, resistance to ampicillin and cephalothin is common in strains of human origin, whereas tetracycline and sulphamethoxazole resistances are frequent in strains of animal origin [92]. In a study involving 54 STEC strains recovered from cattle and pigs, genetic determinants that encode resistance to trimethoprim (dfrA1), tetracycline (tetA and tetB), beta-lactam (blaTEM−1), and aminoglycoside (aac(6)-Ib) were found in the great majority (≥81%) of the isolates, while chloramphenicol resistance gene (cat1) was also carried in more than 50% of the collection [93]. Likewise, in a 15-year surveillance study of STEC in Sweden [94], 70 antibiotic resistance determinants that were associated with 10 different classes of antibiotics were found in 184 STEC isolates, where 50% of these genes were present in all isolates. Six resistance determinants to fluoroquinolone (crp, hns, acrB, marA, mdtM, and emrA) were found to be frequent. Equally, emrE that encodes resistance to multiple antibiotics was associated with STEC O157:H7, whereas fosA7, sat-1, and blaTEM–150 and dfrA5 were associated with non-STEC O157 serotype.
3.4 Population structure of STEC
Genetic relatedness of STEC isolates from different hosts and countries have been studied using different molecular tools that ranged from serotyping, PFGE, conventional MLST, and WGS. Evidence for transmission and dissemination of different STEC serogroups and clones have also been documented. Unlike ETEC that evolved multiple times through clonal expansion, STEC appears to have evolved by parallel evolution. Indeed, phylogenetic analyses of STEC strains have shown that isolates form multiple distinct clonal lineages, where strains with the same serotype and virulence content were nested together in the cluster [95]. STEC strains are spread across E. coli phylogroups and the great majority belonged to phylogroup B1 (Figure 4) [96]. STEC O157:H7 are further delineated into three lineages, I, I/II, and II [97, 98] that are disseminated globally. Lineage I is predominant among clinical isolates of human origin while lineage II is more prevalent in animals [99]. Intra-lineage diversity is apparent as lineages varied in the adherence and virulence determinant expression, Stx-encoding bacteriophage (Stxϕ) insertion sites, stx2 expression, and stress resistance [97]. This intra-clonal diversity is hypothesized to have been a consequence of the global spread of a single clone and geographic expansion [97]. Interestingly, a time-dependent clonal replacement and geographical-dependent clonal expansion of lineages and sub-lineages of STEC O157:H7 have been reported [97, 100]. The STEC O157:H7 lineage I/II that was predominant in human infection in the 1980s in the UK declined and was replaced by sub-lineage Ic in the 1990s. Also, in the past few years, this region has reported the replacement of the dominant sub-lineage (Ic) by sub-lineage IIb, a phenomenon they reported to have been a consequence of the acquisition of prophage encoding stx2a [97, 100].
In a recent study using WGS to understand the population dynamics of 757 STEC O157:H7 isolates from humans and animals from four continents, seven clades were reported and designated as A-G [101]. The most recent common ancestor of the isolates in this study was reported to have originated in the Netherlands in the late 19th century (1890) and then spread to other parts of the world. Although isolates were clustered on a geographical basis, there was an admixture of strains from different hosts suggesting transmission events between them [101]. The pangenome analyses of these isolates also showed that STEC O157:H7 from humans and animals differed in phage-related protein content. The molecular epidemiology of non-STEC O157:H7 is equally important especially considering their roles in outbreaks. From 1995 to 2017, a total of 674 outbreaks by non-O157 STEC strains were reported worldwide, where O26:H11 was predominant during this period [102]. Other serogroups implicated in these outbreaks include O26:H11, O45, O103:H25, O104:H4, O111:H8, O121, and O145:NM [102]. MLST-based phylogenetic analysis of 894 non-STEC isolates from patients over a period of 18 years (2001–2018) in Michigan revealed that the great majority of the isolates (95%) belonged to one clade [103]. Although the information on the evolutionary dynamics of STEC is inexhaustible, studies focusing on identifying new genetic factors associated with ecological adaptation of different lineages are elusive. Further studies should focus on this area.
4. Enteropathogenic E. coli (EPEC)
4.1 An overview of EPEC
Enteropathogenic E. coli (EPEC) is a pathotype that causes infrequent diarrheal diseases in adults and has also been implicated in gastroenteritis outbreaks in children in health care settings [104, 105]. EPEC was the first pathotype described in 1955 to refer to E. coli causing infantile diarrheal and implicated in a few outbreaks between the 1940s and 1950s [106]. Infection from this pathotype is frequent in children under two years living in low- and middle-income countries, and is the second leading cause of death among this age group, amounting to about 1.5 million deaths annually [105]. Like other DEC, the onset of EPEC-related diarrheal is characterized by acute watery stool which if it persists could result in loss of electrolytes and malabsorption of nutrients in children [3, 107]. Infection caused by EPEC strains is not limited to humans as they have also been implicated as a causative agent of diarrheal illness in young calves (Figure 2) [108].
EPEC strains are previously classified solely based on the combination of the three immunogenic structures O, H, and K antigens but the diversity observed for these antigens rendered serotyping unreliable rapid diagnostic tool for this pathotype [17, 107]. However, as recommended in 1987 by World Health Organization, 12 serogroups; O26, O55, O86, O111, O114, O119, O125, O126, O127, O128, O142, and O158 belonged to EPEC pathotype. In addition to six others; O39, O88, O103, O145, O157, and O158 have been classified and belonged to this pathotype although some of these serogroups consist of E. coli strains from different serotypes [108, 109]. EPEC strains are classified as either motile (H+) or non-motile (H−). Among EPEC strains with flagellar associated antigens, H2 and H6 are the most frequent, whereas others that are less common include H7, H8, H9, H12, H21, H27, H25, and H34 [3, 107].
EPEC pathotype is defined based on the carriage of LEE locus that mediates the induction of A/E localized lesions [110], a feature that is shared with some STEC strains. However, the inability to produce Shiga toxins or other enterotoxins differentiate EPEC pathotype from EHEC/STEC strains [3, 10]. Additionally, based on the presence or absence of E. coli adherence factor plasmid (pEAF), EPEC pathotype is sub-grouped into two subtypes; typical (tEPEC) and atypical (aEPEC) [111]. Relative to tEPEC that is regarded to be more virulent, aEPEC group is reported to be highly diverse and more prevalent in diarrheal illness in children [111, 112]. Several O and/or H antigens of aEPEC strains are nontypeable. Of the typeable serogroups belonging to this subtype, O51 is the most frequent followed by five others (O145, O26, O55, O111, and O119) [3]. aEPEC O55:H7 is closely related with STEC O157:H7 and from the evolutionary perspective, the latter is believed to have evolved and diverged 400 years ago from the ancestor of the former [113]. EPEC like other diarrheagenic E. coli pathotypes is transmitted through the fecal-oral route as well as contact with contaminated surfaces or secretions. While humans are believed to be the major reservoir for tEPEC strains, aEPEC strains are present both in healthy individuals and in animals (Figure 2) [111, 112, 114].
4.2 Virulome of EPEC
Since EPEC does not produce Shiga toxin or other enterotoxins, the major feature the pathogenic strains in this pathotype employ is their ability to attach tightly to the host mucosal membrane, destroy microvilli, and induce the formation of lesions (Table 1) [115]. In addition, EPEC carries other genes encoding proteins that have been linked to colonization and adherence to host cells [116, 117].
4.2.1 Colonization and adherence
The defining characteristic of EPEC is the carriage of LEE locus that is essential for inducing A/E lesions, causing localized lesions by attaching closely to the surface of the intestinal epithelial cells. Like some STEC strains, all the EPEC strains carry eae and tir genes as well as T3SS that is able to inject a large number of effector proteins into the host cell [3, 111]. Studies have shown that the presence of LEE locus in EPEC strains is enough to cause infection in the host even in aEPEC-related infection scenario [118].
The ~80 kb pEAF plasmid that defines tEPEC carries per and bfp operons (Table 1) [119, 120]. The per operon (perABC) is plasmid-borne and contains perA that encodes a regulator that activates the transcription of bfp operon that encodes the type IV pili called bundle-forming pilus (BFP) (Figure 3) [119, 120]. The bfpA gene which encodes the bundling of the major structure of BFP and 13 other genes are carried on the pEAF plasmid [116]. The carriage of this plasmid has been described to be essential in the localized adherence of EPEC to intestinal epithelium in the host [118]. tEPEC strains carry lifA gene that encodes lymphocyte inhibitory factor, a large surface protein that is described to promote the intestinal colonization of mice by Citrobacter rodentium [3]. Although pEAF plasmid is absent in aEPEC strains, they often carry virulence determinants typical of STEC strains most likely because they share a common ancestor [113]. Afset et al. [117] identified 12 genes that were statistically associated with aEPEC-related diarrhea in children. Of note are efa1/lifA genes that are located on OI-122, as well as lpfA gene previously reported in STEC [121]. Likewise, astA gene that encodes EAST1, an ST-like toxin that is present in ETEC is also carried by EPEC, being more prevalent in aEPEC than in tEPEC strains implicated in diarrhea [122, 123].
4.3 Antibiotics resistance in EPEC
Although EPEC-related infection could resolve itself or simply by oral rehydration therapy that replenishes the lost fluid, the persistence of this infection may necessitate the use of antibiotics. In this case, especially in adults, the recommended antimicrobial is trimethoprim/sulfamethoxazole, norfloxacin, or ciprofloxacin [124]. However, studies on antibiotic resistance of EPEC strains from different sources and countries have shown high resistance of this pathotype to ampicillin, cefpodoxime, nalidixic acid, trimethoprim, and tetracycline [125, 126]. While resistance to the great majority of these antibiotics is reported to be frequent in tEPEC, trimethoprim resistance is more common in aEPEC strains [127].
In a global study of 185 aEPEC isolates collected from healthy and diarrheal children living in seven sites in sub-Saharan Africa and South Asia, at least 55% of the isolates showed phenotypic resistance to ampicillin, trimethoprim, trimethoprim/sulphamethoxazole, and tetracycline, while streptomycin resistance was reported in 43% of the isolates. Shockingly, more than 50% of the isolates were resistant to three or more of the tested antibiotics [128]. The study also reported point mutations in genes that are associated with resistance to quinolone (gyrA, parC) and nitrofurantoin (nfsA) in addition to over forty different antibiotics resistance genes reported. Equally, more than 50% of the isolates carried at least four resistance determinants that include blaTEM (ampicillin), strA and strB (streptomycin), sul2 (sulphonamides), and dfr genes (trimethoprim/sulfamethoxazole). These resistance determinants were found singly or co-localized on plasmids (pCERC1, pCERC2) or in transposons (Tn6029).
4.4 Population structure of EPEC
The acquisition of LEE and pEAF has been the defining evolutionary phenomenon for EPEC pathotypes [3, 129]. While tEPEC that carries pEAF plasmid is believed to be less diverse, aEPEC is greatly heterogeneous. The loss of pEAF plasmid in aEPEC and its close relatedness with LEE-positive STEC in serotypes, genetic characteristics, virulence properties, and reservoirs make serotype-based lineage definition unreliable [111, 130]. Based on the conventional MLEE and MLST, EPEC strains belong to six clonal lineages (EPEC1–EPEC6) that were represented among the EPEC strains worldwide [129, 131]. The whole genome-based phylogeny reported nine more EPEC lineages designated as EPEC7-EPEC15 [104, 132]. These phylogenomic EPEC lineages belonged to four E. coli phylogroups (A, E, B1, and B2) (Figure 4), where the great majority were found in B1 and B2 [104, 133], suggesting a clear genetic heterogeneity within this pathotype.
The close relatedness of aEPEC to other pathotypes could play a significant role in the diversity within this pathotype. This EPEC subtype can also include tEPEC that have lost the pEAF plasmid and LEE-positive STEC strains that have lost the Stx encoding bacteriophage during transmission events between hosts, within-host evolution, interaction with the host microbiota, or selective pressure in the environment [104, 130]. This could be a possible explanation why some aEPEC strains would cluster with other pathotypes. Indeed, phylogenomic analyses of 106 Brazilian and 221 global aEPEC genomes showed that isolates were clustered into the previously reported phylogroups for this pathotype and phylogroup D. Additionally, 42.5% of the isolates belonged to the four previously defined EPEC lineages [129, 131], while the remaining isolates were found in EPEC11-EPEC14 phylogenomic lineages, suggesting a gradual and continuous clonal expansion of this pathotype [132]. Of note, dissemination of the phylogenomic lineages of EPEC pathotype is not restricted by geography. Conversely, in a multicentre study involving seven sites in developing countries, EPEC isolates from sub-Saharan countries (The Gambia and Kenya) were clustered into two EPEC lineages (EPEC5 and EPEC10) in phylogroup A [104]. Overall, EPEC represents a pathotype that is still undergoing clonal expansion due to the occurrence of novel phylogenomic lineages with distinct accessory gene content and their pathogenic potential.
5. Enteroaggregative E. coli (EAEC)
5.1 An overview of EAEC
Enteroaggregative E. coli (EAEC) is implicated in epidemic diarrheal illnesses, being a causative agent of traveler’s diarrhea, persistent diarrhea in children in EAEC endemic areas, and in immunocompromised patients, particularly in human immunodeficiency virus (HIV) patients [3, 134]. EAEC was first described in 1987 by comparing adherence patterns of E. coli isolates to HEp-2 cells, where it showed a stacked-brick aggregative phenotype. EAEC strains are able to infect the colon and/or small bowel of their host where they disrupt the intestinal epithelium and result in loss of electrolytes, watery diarrhea with or without blood and mucus, vomiting, among other symptoms [134]. Persistent EAEC-related diarrhea could result in chronic intestinal inflammation that induces the production of fecal lactoferrin and interleukin (IL-8), and malabsorption of nutrients [135]. Studies on the development of postinfectious irritable bowel disease syndrome in acute EAEC-related diarrhea have been documented [135] but the role of EAEC is not fully understood.
EAEC strains are identified using a molecular probe AA that hybridizes with a region of pAA plasmid encoding an ATP binding cassette transporter apparatus which translocates dispersion across the bacterial cell membrane [136]. Isolates that carry the aggR gene that encodes autoagglutination that are associated with persistent diarrhea in patients are able to hybridize with the AA probe. In addition, EAEC has a different adherence pattern, and not all HEp-2 adherent EAEC strains isolated from humans with diarrhea carried aggR. Hence, EAEC was classified into two subtypes: typical (aggR positive) and atypical (aggR negative) subtype [134, 137]. Humans are the reservoir for typical EAEC (tEAEC), whereas atypical EAEC (aEAEC) strains have been isolated from young calves, piglets, and horses as well as companion animals, suggesting the role of animals as a reservoir for this subtype (Figure 2) [3].
Although some serotypes including O126:H27, O111:H21, O125, O44:H18 are frequently isolated from EAEC strains, the autoagglutinating phenotype by some EAEC strains complicates the serotyping of this pathotype [3, 138]. In several studies, EAEC strains are often described as nontypeable or as “O?” or O-rough. In a study of EAEC strains from children in Germany, 14 out of 16 isolates that were typeable belonged to different serotypes [139]. Likewise, in a study in the UK, 97 out of 143 EAEC strains that were typeable belonged to more than 40 different O-types [140]. While serotyping is no longer a dependable diagnostic tool for EAEC strains causing diarrheal illness [3, 138], a specific Shiga toxin producing EAEC serotype O104:H4 is associated with a series of outbreaks worldwide [141, 142].
5.2 Virulome of EAEC
EAEC strains that are implicated in diarrheal illness employ several virulence factors that initiate colonization, promote persistence through adherence to mucosal layers of the intestine, and enterotoxin and cytotoxin secretion (Table 1) [134].
5.2.1 Colonization and adherence
EAEC colonizes the intestinal epithelium of the host using aggregative adhesion fimbriae (AAFs) that also activate the host inflammatory responses and afimbrial adhesins [143]. So far, five AAF variants have been described and are encoded by aggA (AAF/I), aafA (AAF/II), agg3A (AAF/III), agg4A (AAF/IV), and agg5A (AAF/V) that are regulated by the transcriptional activator aggR, borne on EAEC plasmid pAA [143]. AggR also regulates the expression of a type VI Secretion System (T6SS) and a chromosomal PAI encoded by aaiA-aaiP operon [144] as well all other virulence genes involved in the aggregation and toxin production in pathogenic strains of EAEC (Figure 3) [143, 144]. However, in EAEC strains where AAF is absent, an aggregate-forming pili (AFP), a type VI pilus that is encoded by afp operon was reported to be responsible for the establishment of a similar aggregative adhesion pattern (Figure 3) [144]. Other virulence determinants associated with colonization and adherence of EAEC include air gene that codifies for an enteroaggregative immunoglobulin repeat protein and capU that encodes a hexosyltransferase homolog, as well as shf and aatA that have been linked to biofilm formation [3, 144].
5.2.2 Enterotoxin and cytotoxin secretion
EAEC produces enterotoxins and cytotoxins including EAST1 and colonization factors encoded by astA and pic genes, respectively [37, 145]. The latter (pic) is often associated with set1A and set1B encoding two subunits of Shigella enterotoxin 1 (ShET1) that are linked to the induction intestinal secretion during infection [145]. This pathotype also carries genes encoding class I cytotoxic SPATE protein family that includes autotransporter proteases encoded by sigA and sepA and plasmid-borne toxin encoded by pet [144, 146]. Also, EAEC strains produce dispersin, an anti-aggregation protein that is encoded by aatPABCD located on plasmid pAA, and promotes the dispersion of bacteria in the mucosal layer of the intestine [147]. A gene hlyE encoding a hemolytic pore-forming toxin that has a cytotoxic effect on cultured cells has also been reported to be present in some EAEC strains, although the role of this gene in the pathogenicity of EAEC is still unclear [3, 148]. Some EAEC strains carry Stx2a phage-encoding Shiga toxin that is associated with HUS in STEC-related infection [141, 146].
The prevalence of the virulence determinants varies with studies and EAEC subtypes [144, 146]. For example, in a study, pic gene was reported to be the most prevalent, present in only 47%, while sepA and sigA were present in less than 15% of the studied isolates [149]. In the study, the authors also noted that pet and pic genes were associated with tEAEC, whereas sepA was associated with aEAEC.
5.3 Antibiotic resistance in EAEC
EAEC-related diseases such as travelers’ diarrhea where antimicrobial therapy is proposed, fluoroquinolones, azithromycin, and rifaximin are often recommended. In immunocompromised patients that require chemoprophylaxis, fluoroquinolones are also considered [150]. For Shiga toxin producing EAEC O104: H4 related infections, azithromycin which has been shown to inhibit stx expression in in-vitro assay is seldomly used [3, 150].
Although a highly successful treatment rate is achieved with these antibiotics, EAEC strains that are resistant to multiple antibiotics have emerged in different regions [150]. Studies on the resistance of EAEC strains from Southeast Asia, India, Africa, and Latin America with travelers’ diarrhea showed that more than 50% of the isolates were resistant to ampicillin, sulphamethoxazole, and tetracycline [150, 151]. In a similar study in Iran, 78% and 60% of the extended-spectrum beta-lactamase (ESBL) producing EAEC strains carried the transposable blaTEM and blaCTX-M genes, respectively [152]. Also, plasmid-mediated quinolone resistance (PMQR) genes (qnr) that encode resistance to quinolone have been identified in EAEC in different studies [153, 154]. In England, among the 155 EAEC strains from diarrhea patients in 2015–2016 [155] showing antibiotic-resistant phenotypes, 43 genetic determinants that encode resistance to seven different classes of antibiotics were identified, with blaTEM-1 being the most common (40%) followed by sul2 (37%) and strA-strB (32%). Undoubtedly, the rise in antibiotic resistance in this pathotype should be a concern for public health.
5.4 Population structure of EAEC
EAEC subtypes are defined based on the presence of virulence plasmid pAA that carries aggR gene that regulates the expression of other virulence determinants located on the plasmid. This and the high serotype diversity, as well as other accessory genes contribute to the high heterogeneity noted for this pathotype. An earlier study on the phylogenetic analysis of EAEC revealed that isolates belonged to multiple lineages [156]. A similar observation was noted with MLST where 150 Nigerian EAEC strains were clustered into 96 STs [157]. Indeed, EAEC strains are known to belong and spread across four E. coli phylogroups (A, B1, B2, and D) (Figure 4) with diverse serotypes [144, 156].
In a recent study [146], of the 97 EAEC strains analyzed using MLST, 42% were reported to belong to phylogroup B1, while the majority of the few strains that belonged to phylogroup A lack the AAF-associated genes. Although serotype diversity is high in this pathotype, this study also noted that EAEC strains that belonged to phylogroup D were clustered into three serotype-specific lineages (lineage 1–3). All strains in lineage 1 were O166:H15 and belonged to ST349, lineage 2 consisted of serogroups O44, O73, and O17/O77 in combination with either H18 or H34 and ST130, while lineage 3 carried O153:H30 serotype and ST38 [146]. Contrarily, in India, EAEC strains implicated in diarrhea were more prevalent in phylogroup D [158] suggesting that the diversity in the pathotype is not limited by geography. While EAEC subtypes are believed to differ in their virulence determinants content, this hypothesis and comparative phylogenetic analysis of aEAEC and tEAEC are underexplored. Also, large-scale phylogenomic and phylogeographic analyses of this pathotype are scarce. Further studies should focus on this.
6. Entero-invasive E. coli (EIEC)
6.1 An overview of EIEC
Enteroinvasive E. coli (EIEC) pathotype causes bacillary dysentery in humans worldwide characterized by abdominal cramps, bloody and mucous diarrhea [159]. The incidence of EIEC-related diseases varies by geographic region but is highly frequent in developing countries. In developed countries, EIEC-related infections are mainly travelers’ diarrheal cases in people with recent travel history to endemic regions [160]. The first EIEC strain belonging to serotype O124 was reported in 1947 [161]. In the later years, some of the bacterial species implicated in dysentery that were previously classified as Shigella were renamed as EIEC [162]. EIEC and Shigella spp. share several serogroups, phenotypic and other genotypic characteristics, which often makes it challenging to discriminate between the two genera in clinical samples. Like some Shigella spp., most EIEC strains are non-motile and lack the ability to decarboxylate lysine or ferment lactose [3]. EIEC invades the human intestinal epithelial layer where it induces dysentery syndrome that is characterized by watery stool containing blood, mucus, and leukocytes, symptoms that are similar to those presented by Shigella spp. associated infection (Figures 2 and 3) [159].
At least, 20 serotypes have been assigned to this pathotype [159] among which some of the EIEC-associated O antigens including O28, O112ac, O121, O124, O143, O144, O152, and O167, are identical to O antigens present in Shigella spp. [3, 159]. Humans are the major reservoir of EIEC strains and transmission occurs through the fecal-oral route from the ingestion of contaminated foods or water and person-to-person contact [159, 160]. The incidence rate and morbidity for EIEC are less or underreported but it appears to follow a similar trend as Shigella [3, 159]. Although EIEC strains cause sporadic cases of infection, they are also implicated in outbreaks. Of note are outbreaks of EIEC linked to O96:H19 strain that was traced to cooked vegetables and salads that were contaminated by asymptomatic food handlers in 2012 and 2014 in Italy [163] and the United Kingdom [164], respectively. Recently, the first case of EIEC outbreak in the US in about half a century was caused by EIEC serotype O8:H19 [160].
6.2 Virulome of EIEC
EIEC strains cause infection in humans by their ability to invade the colon mucosa layer with the expression of essential virulence determinants that mediate colonization, adherence, and invasion of the intestinal epithelial cells of the host (Table 1). These genes that are also shared with Shigella are located on the chromosome or virulence plasmid.
6.2.1 Colonization and adherence
The colonization, adherence, and invasion of intestinal epithelial cells by EIEC are mediated by genetic factors encoded by genes on a plasmid, pINV. pINV is a virulence plasmid found in EIEC that encodes the type III secretion system necessary for attachment, invasion of the host cell, and intercellular spread. This plasmid is structurally and functionally similar to those in Shigella strains [159], and with the replication (rep) and conjugation (tra) regions in IncFIIA plasmids. pINV had large deletions in the tra region which makes it incapable of self-transfer by conjugation but can be mobilized by other conjugative plasmids. Among the numerous functional insertion sequences present in this plasmid is the IS1111 family, but only defective copies of the IS family are found in Shigella pINV plasmids [159]. pINV carries a PAI-structure that is composed of gene clusters encoding a T3SS apparatus (Mxi and Spa), its effector proteins (IpaB, IpaC, and IpaD) with their chaperons (IpgA, IpgC, IpgE, and Spa15), and two global transcriptional regulators (VirB and MxiE) that activate and regulate the expression of most of the virulence genes [3, 159]. All T3SS effectors are carried on the pINV except for a few effector proteins of the IpaH family that are chromosomal (Figure 3).
Also carried on pINV are genes that encode IcsA, a protein that facilitates the bacterial movement inside the cytoplasm, VirA, a GTPase-activating protein, and RnaG, a small RNA that negatively control the expression of icsA gene [159, 165], as well as the gene encoding OspG and OspF proteins which facilitate the evasion of the host innate immune response. All EIEC isolates are reported to carry this plasmid as it is essential for the pathogenesis and pathoadaptation of this pathotype. However, loss of this genetic element has been reported in some EIEC strains [159, 165].
6.2.2 Cytotoxins production
EIEC strains also carry a plasmid-borne gene, sen that mediates a novel 63-kDa enterotoxin (ShET2) [166]. A mutation in this gene was reported to cause a substantial loss in the enterotoxic ability of EIEC strain. Although the role of this gene in the pathogenesis of EIEC is not fully understood, toxins are known to be important in the induction of watery diarrhea during E. coli infection. Additionally, plasmid encoding enterotoxigenic and cytotoxigenic factors namely pic, sepA, sigA, and sat that belong to SPATEs family and that are reported to contribute to intestinal fluid accumulation in an animal model are carried by EIEC strains. Nonetheless, these genes are not carried by all EIEC strains. Two different studies on the prevalence of the virulence genes among EIEC reported that sen, sigA, and pic were found in at least 70%, 64%, and 27% of the isolates, respectively [167, 168], whereas sat gene was found only in 15% of the collection [167].
6.3 Antibiotic resistance in EIEC
EIEC-related infection is self-limiting that could be managed with rehydration to replenish the loss electrolyte. Zinc supplementation and nutritional therapy with iron-rich green plantain have also been shown to reduce the severity and the duration of diarrheal illness. However, in rare cases of severe symptoms antimicrobial treatment therapy has been reported to be effective [3, 10]. Since Shigella and EIEC present similar symptoms and are often misdiagnosed, similar antimicrobials include azithromycin (macrolide), ceftriaxone, (cephalosporin), and ciprofloxacin (fluoroquinolone) are recommended [3, 159].
Like other E. coli pathotypes and Shigella, there is an emergence of multidrug-resistant EIEC strains. In a study of EIEC isolates from adults with enteric infection in Cameroon, high resistance to ampicillin and sulfamethoxazole-trimethoprim was noted in 57.14% and 71.43%, respectively. Resistance determinants to ampicillin (blaTEM and blaOxa) were found in 28.57% of the isolates. Additionally, cat1 and cat2 genes were noted in chloramphenicol resistant strains while tetA, tetB encoding resistance to tetracycline, dfr12, dfr7, dfr1a to sulphamethoxazole-trimethoprim, and sul1 gene to sulfonamide were present in more than 85% of the EIEC isolates [169]. In a large-scale study of Shigella and EIEC isolates from eight countries in four continents between 1971 and 1999, 48% of EIEC isolates were resistant to tetracycline [170]. In another study, an EIEC O164 strain isolated from a traveler with diarrhea in Japan was found to be resistant to streptomycin, spectinomycin, co-trimoxazole, and ampicillin, with reduced susceptibility to ciprofloxacin [171]. In this strain, resistance determinant for trimethoprim (dfrXII), streptomycin and spectinomycin (aadA2), and an ORF of unknown function was carried on a class 1 integron located on a transferable plasmid. While ampicillin resistance gene blaTEM was detected, the reduced susceptibility to ciprofloxacin was reported to be due to a single mutation P158-to-S in parC.
6.4 Population structure of EIEC
EIEC pathotype is diverse and highly specialized due to the carriage of large virulence plasmid, a genetic element that is shared with Shigella. The pINV plasmid that is the hallmark of EIEC lacks the ability for autonomous horizontal transfer. Although there is no consensus on the evolution of pINV in Shigella/EIEC, it has been hypothesized that this genetic element was probably acquired in an ancestral E. coli prior to the diversification of the two bacterial species and the emergence of different Shigella/EIEC lineages. Conversely, Shigella/EIEC strains could have evolved from different E. coli strains that had acquired the pINV independently from other pINV-carrying Shigella/EIEC or from an unknown donor [172].
A phylogenetic analysis of 32 EIEC strains based on four housekeeping genes (trpA, trpB, pabB, and putP) revealed four clusters (clusters 4–7) where most of the O antigens were found in a single cluster [173]. EIEC cluster 4 comprised strains with serotype O28, O29, O124, O136, and O164. Serotypes O124, O135, O152, and O164 belonged to cluster 5, and O143 and O167 to cluster 6 while cluster 7 had only O144 [173]. This is similar to a SNP-based phylogeny described in another study [174]. WGS alignment-based phylogeny of 20 EIEC isolates revealed that the great majority of the strains belonged to three distinct EIEC lineages (lineage 1–3) that belonged to three different E. coli phylogroups (A, B1, and E) (Figure 4). All the EIEC strains in lineage 1 (phylogroup E) were all serotype O143:H26, whereas, in other lineages the serotypes were diverse. EIEC lineage 3 (phylogroup B1) was reported to be globally disseminated as the strains from six different countries were clustered together in this lineage [175].
Insertion sequences were recently reported to contribute to the population structure of EIEC. A recent study [176] on the evolutionary dynamics of Shigella and EIEC lineages identified the genetic factors driving strain-to-strain variation within each population and contributing to functional gene loss within and between species. In the study, the author found that all Shigella and EIEC lineages had higher IS copy numbers relative to other E. coli pathotypes indicative of IS expansion in these lineages. The authors also found that Shigella and EIEC lineages carried the same five ISs (IS1, IS2, IS4, IS911, and IS600) indicative of a parallel expansion of these IS types, although at a high degree in Shigella. The data also suggests that Shigella and EIEC lineages underwent an expansion of their native IS1 alleles and that pINV is a potential source for the introduction of other ISs (IS2, IS4, IS600, and IS911) that are rare in E. coli into Shigella and EIEC lineages [176].
In a comparative pangenome analysis of EIEC with Shigella and other E. coli pathotypes, seven gene clusters were identified to be enriched in EIEC strains but absent in all other E. coli pathotypes and Shigella strains. These included genes that encode a putative pyruvate kinase, a periplasmic protein, and some uncharacterized proteins. However, when Shigella isolates were excluded, the authors identified 96 gene clusters that were present in more than half of the EIEC strains. A total of 87 gene clusters were reported when EIEC and Shigella genomes combined were compared to other E. coli pathotypes. Among these were plasmid-associated genes encoding a hypothetical toxin-antitoxin system and putative proteins hypothesized to be involved in conjugal transfer [175].
The EIEC lineages were reported to have distinct phenotypic and genotypic features. Lan et al. [173] reported that EIEC strains belonging to cluster 4 lack mucate fermentation ability, whereas strains in cluster 6 were able to utilize acetate and ferment mucate [173]. Likewise, Hazen et al. [175] identified up to 155 gene clusters that were exclusive in EIEC strains belonging to one phylogroup. Additionally, 12–155 gene clusters were also reported to be lineage-specific in the EIEC pathotype [175]. Protein-encoding genes that are linked to transcriptional regulation, metabolism, and transport, and a colicin were exclusive in EIEC lineage 1, whereas genes that encode membrane protein, the aerobactin siderophore receptor, and hypothetical proteins were exclusive for EIEC lineage 2. Genes encoding several transcriptional regulators and hypothetical proteins were limited to EIEC lineage 3 [175].
7. Diffusely adherent E. coli (DAEC)
7.1 An overview of DAEC
Diffusely adherent E. coli (DAEC) pathotype is a group of E. coli causing diarrhea that can attach to host cells but not in a localized or A/E adherence pattern [3]. E. coli strains belonging to this pathotype binds to the entire surface of the epithelial HEp-2 cells in a scattered pattern termed diffuse adherence. Although the adherence pattern is unique, this pathotype is difficult to classify or identify, a possible reason for the scarce epidemiological studies on this group [177].
DAEC is widespread and associated with diarrhea in both developing and industrialized countries around the world [3]. DAEC strains are associated with watery diarrhea in children under 5 years and can persist resulting in an increase in severity of disease in this age group [177]. DAEC has also been implicated in extraintestinal infections such as UTI, pregnancy complications [3, 177]. It has been speculated that the asymptomatic carriage of DAEC by this age group and adults can lead to chronic inflammatory colon disease such as Crohn’s disease [3, 177]. Meanwhile, there is no universal detection method for this pathotype but based on DNA hybridization of fimbrial encoding daaC gene probe and adherence pattern to HEp-2 cells of 221 diarrheagenic E. coli from different age-groups in Brazil [178], DAEC was identified and shown to be associated with diarrhea in children under 12 months of age in this region. The authors also noted that the presence of DAEC in younger children was not associated with diarrhea, suggesting that the association would probably be based on geographic regions [178]. The asymptomatic carriage by different age groups and the lack of epidemiological data from different regions undermines the development of a universal identification method for this pathotype.
While it is unclear how DAEC is transmitted or its reservoir, the fact that there are asymptomatic carriers could suggest humans as the main reservoir and the fecal-oral route as the primary means of transmission (Figure 2). Information regarding serotypes associated with DAEC is scarce. A study of 112 DAEC isolates from diarrheal and asymptomatic individuals in Brazil reported 45 different serotypes, of which 19 were exclusive in patients with diarrhea [179], whereas in another study [180] the serotypes were nontypeable.
7.2 Virulome of DAEC
DAEC strains infect the intestinal epithelium of the host by expressing surface-exposed adhesins that mediate colonization and attachment which allow them to resist host clearance mechanisms [177]. There are several virulence factors that mediate this process, and they include fimbria or afimbrial structures, adhesins, and secretion of cytotoxic toxins that promote the invasion of the host cells (Table 1) [177].
7.2.1 Colonization and adherence
DAEC pathotype carries genes that encode Afa/Dr adhesins [3, 177]. Afa/Dr family includes Afa, Dr, and F1845 adhesins that are both afimbrial (such as AfaE-I and AfaE-III), and fimbrial (such as F1845 and Dr) adhesive structures on the bacterial surface encoded by the afa, dra, and daa operons, respectively [177, 181]. These adhesins have been found not only in DAEC but also in UPEC (Uropathogenic E. coli), indicating that strains that produce Afa/Dr adhesins may cause both intestinal and extraintestinal infections. Afa/Dr adhesins bind to human decay-accelerating factor (hDAF) and carcinoembryonic antigen-related cell adhesion molecules that induce receptor clustering resulting in a partial internalization of bacterial cells (Figure 3). These adhesins can induce the production of cytokine IL-8 and result in intestinal inflammation, loss of microvilli structure, and watery diarrhea [177]. There are two different subclasses of atypical DAEC; a subclass that contains all the adhesins typical of the Afa/Dr family of adhesins in another E. coli pathotype such as diffusely adherent EPEC, while the other subclass does not bind hDAF and expresses a different array of adhesins on its surface, including AfaE-VII, AfaE-VIII, AAF-I, AAF-II, and AAF-III and still able to induce proinflammation [177].
The prevalence of the genes constituting the operons that encode the Afa/Dr adhesins have been reported to vary in DAEC pathotype. In a study, the prevalence of the Afa/Dr adhesin family encoding genes afaE-1, afaE-2, afaE-3, afaE-5 and daaE were reported in 64.3%, 14.2%, 28.6%, 21.5% and 21.5% of DAEC isolates, respectively [182], while in another study [183], the prevalence of these genes were 44%, 10%, 2%, 2% and 6%, respectively.
7.2.2 Secretion of cytotoxins
DAEC secretes a class I SPATE toxin that is called secreted autotransporter toxin (Sat), encoded by sat gene. Sat is reported to have enterotoxic activity in an animal model, and mediate the induction of fluid accumulation, loss of microvilli, inflammation, and polymorphonuclear lymphocytes (PMNL) infiltration, like the LT effect of ETEC (Figure 3) [184]. Although sat gene is reported to be equally expressed in DAEC strains from diarrheal and asymptomatic adults, this gene is significantly associated with DAEC-related diarrhea in children [183]. For example, in two studies, sat gene was identified in 44–63% of DAEC strains collected from children with diarrhea while it was found in 0–20% of DAEC strains from asymptomatic children [183, 184, 185]. Noteworthy, sat gene is not exclusive for DAEC pathotype. In fact, it is prevalent in other E. coli pathotypes including EAEC and UPEC [186]. Other virulence factors that have been reported in DAEC include pet [187], astA [187], and senB [188] genes that encode enterotoxins and hlyE gene that encodes alpha-hemolysin [186]. However, the role of these genes in the pathogenesis of DAEC still remains unclear.
7.3 Antibiotic resistance in DAEC
Oral rehydration solution therapy is the only recommended treatment for DAEC-related watery diarrhea. However, there are reports of antibiotic resistance in this pathotype. In a study of 112 DAEC strains isolated from children with watery diarrhea in Brazil [179], all DAEC isolates were susceptible to five antibiotics including gentamicin, ofloxacin, and nalidixic acid while 70% were resistant to three or more antibiotics and 50% showed resistance to either ampicillin, co-trimoxazole, streptomycin, sulfonamide, or tetracycline. Additionally, 20% of the strains were resistant to chloramphenicol [179]. A similar observation was noted in a study from Iran where 75–100% of DAEC strains from pediatric diarrhea were resistant to ampicillin, cefotaxime, and trimethoprim-sulfamethoxazole [182].
7.4 Population structure of DAEC
DAEC is a heterogeneous group that has also been implicated in extraintestinal infections such as UTI. Despite its implication in diarrhea in children, studies on its population structure are limited. The few studies available on the phylogenetic analysis of DAEC strains using MLEE reported that they are distributed among all of the phylogroups [47, 156, 189]. Conversely, a study of 31 DAEC strains from diarrhea and asymptomatic carriers in Peru reported that 87% of the isolates belonged to phylogroup D [190]. A large-scale genomic analysis of DAEC strains would be important to understand the population structure, determine dissemination and transmission dynamics of genetic lineages of this pathotype, as well as identify novel virulence determinants and other genetic factors that contribute to its pathoadaptation in the intestinal epithelium.
8. Conclusion
Much progress has been made on the biology and the genomic epidemiology of diarrheagenic E. coli pathotypes since the development of WGS technologies. In particular, there is a notable advancement in the timely detection of outbreaks and the understanding of the population structure of some of the DEC pathotypes. However, the distinct phenotypes underlying the genomic signatures that drive the evolution of pathogenic E. coli are not fully understood. Large-scale genomic analyses of different E. coli pathotypes are scarce, hence, the genetic factors that define each pathovar and specific lineages are still underexplored. These should form the direction for future studies to better understand the evolutionary dynamics of E. coli pathotypes.
\n',keywords:"E. coli, pathotypes, antimicrobial resistance, genetic lineages, pathogenicity, genomics",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80331.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80331.xml",downloadPdfUrl:"/chapter/pdf-download/80331",previewPdfUrl:"/chapter/pdf-preview/80331",totalDownloads:54,totalViews:0,totalCrossrefCites:0,dateSubmitted:"August 27th 2021",dateReviewed:"November 9th 2021",datePrePublished:"February 3rd 2022",datePublished:null,dateFinished:"February 3rd 2022",readingETA:"0",abstract:"Escherichia coli is a commensal of the gastrointestinal tract of humans and animals, and a leading cause of gastroenteritis, bloodstream, and urinary tract infection, among others. Pathogenic E. coli causing diarrhea is delineated into six different types (pathotypes) based on the type of infection they cause. While these pathotypes have similar mechanisms to colonize the intestinal epithelial layers and cause diseases, they differ in their capacity to acquire virulence, resistance determinants, and other accessory genes essential for niche adaptation. The advent of whole-genome sequencing technologies has greatly enhanced our understanding of the physiology, emergence, and global spread of multidrug-resistant and pathogenic clones of E. coli. In this chapter, we provided a snapshot of the resistome and virulome, as well as their contributions to the ecological adaptation, evolution, and dissemination of E. coli pathotypes.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80331",risUrl:"/chapter/ris/80331",signatures:"Opeyemi U. Lawal, Valeria R. Parreira and Lawrence Goodridge",book:{id:"10894",type:"book",title:"Escherichia coli",subtitle:null,fullTitle:"Escherichia coli",slug:null,publishedDate:null,bookSignature:"Dr. Marjanca Starčič Erjavec",coverURL:"https://cdn.intechopen.com/books/images_new/10894.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-870-5",printIsbn:"978-1-83969-869-9",pdfIsbn:"978-1-83969-871-2",isAvailableForWebshopOrdering:!0,editors:[{id:"58980",title:"Dr.",name:"Marjanca",middleName:null,surname:"Starčič Erjavec",slug:"marjanca-starcic-erjavec",fullName:"Marjanca Starčič Erjavec"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Enterotoxigenic E. coli (ETEC)",level:"1"},{id:"sec_2_2",title:"2.1 An overview of ETEC",level:"2"},{id:"sec_3_2",title:"2.2 Virulome of ETEC",level:"2"},{id:"sec_3_3",title:"2.2.1 Colonization and adhesion",level:"3"},{id:"sec_4_3",title:"2.2.2 Enterotoxin secretion",level:"3"},{id:"sec_6_2",title:"2.3 Antibiotic resistance in ETEC",level:"2"},{id:"sec_7_2",title:"2.4 Population structure of ETEC",level:"2"},{id:"sec_9",title:"3. Shiga toxin-producing E. coli (STEC)",level:"1"},{id:"sec_9_2",title:"3.1 An overview of STEC",level:"2"},{id:"sec_10_2",title:"3.2 Virulome of STEC",level:"2"},{id:"sec_10_3",title:"3.2.1 Colonization and adherence",level:"3"},{id:"sec_11_3",title:"3.2.2 Cytotoxic toxin production",level:"3"},{id:"sec_13_2",title:"3.3 Antibiotic resistance in STEC",level:"2"},{id:"sec_14_2",title:"3.4 Population structure of STEC",level:"2"},{id:"sec_16",title:"4. Enteropathogenic E. coli (EPEC)",level:"1"},{id:"sec_16_2",title:"4.1 An overview of EPEC",level:"2"},{id:"sec_17_2",title:"4.2 Virulome of EPEC",level:"2"},{id:"sec_17_3",title:"4.2.1 Colonization and adherence",level:"3"},{id:"sec_19_2",title:"4.3 Antibiotics resistance in EPEC",level:"2"},{id:"sec_20_2",title:"4.4 Population structure of EPEC",level:"2"},{id:"sec_22",title:"5. Enteroaggregative E. coli (EAEC)",level:"1"},{id:"sec_22_2",title:"5.1 An overview of EAEC",level:"2"},{id:"sec_23_2",title:"5.2 Virulome of EAEC",level:"2"},{id:"sec_23_3",title:"5.2.1 Colonization and adherence",level:"3"},{id:"sec_24_3",title:"5.2.2 Enterotoxin and cytotoxin secretion",level:"3"},{id:"sec_26_2",title:"5.3 Antibiotic resistance in EAEC",level:"2"},{id:"sec_27_2",title:"5.4 Population structure of EAEC",level:"2"},{id:"sec_29",title:"6. Entero-invasive E. coli (EIEC)",level:"1"},{id:"sec_29_2",title:"6.1 An overview of EIEC",level:"2"},{id:"sec_30_2",title:"6.2 Virulome of EIEC",level:"2"},{id:"sec_30_3",title:"6.2.1 Colonization and adherence",level:"3"},{id:"sec_31_3",title:"6.2.2 Cytotoxins production",level:"3"},{id:"sec_33_2",title:"6.3 Antibiotic resistance in EIEC",level:"2"},{id:"sec_34_2",title:"6.4 Population structure of EIEC",level:"2"},{id:"sec_36",title:"7. Diffusely adherent E. coli (DAEC)",level:"1"},{id:"sec_36_2",title:"7.1 An overview of DAEC",level:"2"},{id:"sec_37_2",title:"7.2 Virulome of DAEC",level:"2"},{id:"sec_37_3",title:"7.2.1 Colonization and adherence",level:"3"},{id:"sec_38_3",title:"7.2.2 Secretion of cytotoxins",level:"3"},{id:"sec_40_2",title:"7.3 Antibiotic resistance in DAEC",level:"2"},{id:"sec_41_2",title:"7.4 Population structure of DAEC",level:"2"},{id:"sec_43",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Frazão N, Sousa A, Lässig M, Gordo I. Horizontal gene transfer overrides mutation in Escherichia coli colonizing the mammalian gut. Proceedings of the National Academy of Sciences. 2019;116:17906-17915'},{id:"B2",body:'Capps KM, Ludwig JB, Shridhar PB, Shi X, Roberts E, et al. Identification, Shiga toxin subtypes and prevalence of minor serogroups of Shiga toxin-producing Escherichia coli in feedlot cattle feces. Scientific Reports. 2021;11. Epub ahead of print 21 April 2021. DOI: 10.1038/s41598-021-87544-w'},{id:"B3",body:'Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, et al. Recent advances in understanding enteric pathogenic Escherichia coli. Clinical Microbiology Reviews. 2013;26:822-880'},{id:"B4",body:'Kim KS. Human meningitis-associated Escherichia coli. EcoSal Plus. 2016;7. Epub ahead of print May 2016. DOI: 10.1128/ecosalplus.ESP-0015-2015'},{id:"B5",body:'Devasia RA, Jones TF, Ward J, Stafford L, Hardin H, et al. Endemically acquired foodborne outbreak of enterotoxin-producing Escherichia coli serotype O169:H41. The American Journal of Medicine. 2006;119:168.e7-168.e10'},{id:"B6",body:'Troeger C, Blacker BF, Khalil IA, Rao PC, Cao S, et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet Infectious Diseases. 2018;18:1211-1228'},{id:"B7",body:'Winstead A, Hunter JC, Griffin PM. Escherichia coli, Diarrheagenic. In: Chapter 4—2020 Yellow Book | Travelers’ Health | CDC. Available from: https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/escherichia-coli-diarrheagenic. [Accessed: 16 August 2021]'},{id:"B8",body:'Poirel L, Madec J-Y, Lupo A, Schink A-K, Kieffer N, et al. Antimicrobial Resistance in Escherichia coli. Microbiology Spectrum. 2018;6. Epub ahead of print 27 July 2018. DOI: 10.1128/microbiolspec.ARBA-0026-2017'},{id:"B9",body:'Irving SE, Choudhury NR, Corrigan RM. The stringent response and physiological roles of (pp)pGpp in bacteria. Nature Reviews. Microbiology. 2021;19:256-271'},{id:"B10",body:'Kaper JB, Nataro JP, Mobley HLT. Pathogenic Escherichia coli. Nature Reviews. Microbiology. 2004;2:123-140'},{id:"B11",body:'Beutin L, Delannoy S, Fach P. Genetic diversity of the fliC genes encoding the flagellar antigen H19 of Escherichia coli and application to the specific identification of enterohemorrhagic E. coli O121:H19. Applied and Environmental Microbiology. 2015;81:4224-4230'},{id:"B12",body:'Ejrnaes K, Sandvang D, Lundgren B, Ferry S, Holm S, et al. Pulsed-field gel electrophoresis typing of Escherichia coli strains from samples collected before and after pivmecillinam or placebo treatment of uncomplicated community-acquired urinary tract infection in women. Journal of Clinical Microbiology. 2006;44:1776'},{id:"B13",body:'Pupo GM, Lan R, Reeves PR, Baverstock PR. Population genetics of Escherichia coli in a natural population of native Australian rats. Environmental Microbiology. 2000;2:594-610'},{id:"B14",body:'Naseer U, Olsson-Liljequist BE, Woodford N, Dhanji H, Cantón R, et al. Multi-locus variable number of tandem repeat analysis for rapid and accurate typing of virulent multidrug resistant Escherichia coli clones. PLoS One. 2012;7:e41232'},{id:"B15",body:'Adiri RS, Gophna U, Ron EZ. Multilocus sequence typing (MLST) of Escherichia coli O78 strains. FEMS Microbiology Letters. 2003;222:199-203'},{id:"B16",body:'Schürch AC, Arredondo-Alonso S, Willems RJL, Goering RV. Whole genome sequencing options for bacterial strain typing and epidemiologic analysis based on single nucleotide polymorphism versus gene-by-gene–based approaches. Clinical Microbiology and Infection. 2018;24:350-354'},{id:"B17",body:'Joensen KG, Scheutz F, Lund O, Hasman H, Kaas RS, et al. Real-time whole-genome sequencing for routine typing, surveillance, and outbreak detection of verotoxigenic Escherichia coli. Journal of Clinical Microbiology. 2014;52:1501-1510'},{id:"B18",body:'Crofts AA, Giovanetti SM, Rubin EJ, Poly FM, Gutiérrez RL, et al. Enterotoxigenic E. coli virulence gene regulation in human infections. Proceedings of the National Academy of Sciences. 2018;115:E8968-E8976'},{id:"B19",body:'Gupta SK, Keck J, Ram PK, Crump JA, Miller MA, et al. Part III. Analysis of data gaps pertaining to enterotoxigenic Escherichia coli infections in low and medium human development index countries, 1984-2005. Epidemiology and Infection. 2008;136:721-738'},{id:"B20",body:'Hartadi EB, Effendi MH, Plumeriastuti H, Sofiana ED, Wibisono FM, et al. A review of enterotoxigenic Escherichia coli infection in piglets: Public health importance. Systematic Reviews in Pharmacy. 2020;11:12'},{id:"B21",body:'Pattabiraman V, Katz LS, Chen JC, McCullough AE, Trees E. Genome wide characterization of enterotoxigenic Escherichia coli serogroup O6 isolates from multiple outbreaks and sporadic infections from 1975-2016. PLoS One. 2018;13:e0208735'},{id:"B22",body:'Begum YA, Talukder KA, Azmi IJ, Shahnaij M, Sheikh A, et al. Resistance pattern and molecular characterization of enterotoxigenic Escherichia coli (ETEC) strains isolated in Bangladesh. PLoS One. 2016;11:e0157415'},{id:"B23",body:'Qadri F, Svennerholm A-M, Faruque ASG, Sack RB. Enterotoxigenic Escherichia coli in developing countries: Epidemiology, microbiology, clinical features, treatment, and prevention. Clinical Microbiology Reviews. 2005;18:465-483'},{id:"B24",body:'Sahl JW, Sistrunk JR, Baby NI, Begum Y, Luo Q, et al. Insights into enterotoxigenic Escherichia coli diversity in Bangladesh utilizing genomic epidemiology. Scientific Reports. 2017;7:3402'},{id:"B25",body:'Sánchez J, Holmgren J. Virulence factors, pathogenesis and vaccine protection in cholera and ETEC diarrhea. Current Opinion in Immunology. 2005;17:388-398'},{id:"B26",body:'Duan Q, Yao F, Zhu G. Major virulence factors of enterotoxigenic Escherichia coli in pigs. Annales de Microbiologie. 2012;62:7-14'},{id:"B27",body:'Vipin Madhavan TP, Sakellaris H. Colonization factors of enterotoxigenic Escherichia coli. In: Advances in Applied Microbiology. Amsterdam, The Netherlands: Elsevier. pp. 155-197'},{id:"B28",body:'Chung S, Kwon T, Bak Y-S, Park JJ, Kim C-H, et al. Comparative genomic analysis of enterotoxigenic Escherichia coli O159 strains isolated from diarrheal patients in Korea. Gut Pathogens. 2019;11:9'},{id:"B29",body:'Joffré E, von Mentzer A, Svennerholm A-M, Sjöling Å. Identification of new heat-stable (STa) enterotoxin allele variants produced by human enterotoxigenic Escherichia coli (ETEC). International Journal of Medical Microbiology. 2016;306:586-594'},{id:"B30",body:'Bhakat D, Mondal I, Chatterjee NS. EatA, a non-classical virulence factor, of Enterotoxigenic Escherichia coli (ETEC) is modulated by the host factors during pathogenesis. International Journal of Infectious Diseases. 2020;101:3-4'},{id:"B31",body:'Kumar P, Luo Q, Vickers TJ, Sheikh A, Lewis WG, et al. EatA, an immunogenic protective antigen of enterotoxigenic Escherichia coli, Degrades Intestinal Mucin. Infection and Immunity. 2014;82:500-508'},{id:"B32",body:'Liu F, Yang X, Wang Z, Nicklasson M, Qadri F, et al. Draft genomes of four enterotoxigenic Escherichia coli (ETEC) clinical isolates from China and Bangladesh. Gut Pathogens. 2015;7:10'},{id:"B33",body:'Ajami NJ, Youmans BP, Highlander SK, DuPont HL, Petrosino JF, et al. Development and accuracy of quantitative real-time polymerase chain reaction assays for detection and quantification of enterotoxigenic Escherichia coli (ETEC) heat labile and heat stable toxin genes in travelers’ diarrhea samples. The American Journal of Tropical Medicine and Hygiene. 2014;90:124-132'},{id:"B34",body:'Wang H, Zhong Z, Luo Y, Cox E, Devriendt B. Heat-stable enterotoxins of enterotoxigenic Escherichia coli and Their impact on host immunity. Toxins. 2019;11:24'},{id:"B35",body:'Zhu Y, Luo Q, Davis SM, Westra C, Vickers TJ, et al. Molecular determinants of enterotoxigenic Escherichia coli heat-stable toxin secretion and delivery. Infection and Immunity. 2018;86:15'},{id:"B36",body:'Jobling MG, Holmes RK. Type II heat-labile enterotoxins from 50 diverse Escherichia coli isolates belong almost exclusively to the LT-IIc family and may be prophage encoded. PLoS One. 2012;7:e29898'},{id:"B37",body:'Ménard L-P, Dubreuil JD. Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1): A new toxin with an old twist. Critical Reviews in Microbiology. 2002;28:43-60'},{id:"B38",body:'Turner SM, Scott-Tucker A, Cooper LM, Henderson IR. Weapons of mass destruction: Virulence factors of the global killer Enterotoxigenic Escherichia coli. FEMS Microbiology Letters. 2006;263:10-20'},{id:"B39",body:'Dubreuil JD. EAST1 toxin: An enigmatic molecule associated with sporadic episodes of diarrhea in humans and animals. Journal of Microbiology. 2019;57:541-549'},{id:"B40",body:'Zhang W, Berberov EM, Freeling J, He D, Moxley RA, et al. Significance of heat-stable and heat-labile enterotoxins in porcine colibacillosis in an additive model for pathogenicity studies. Infection and Immunity. 2006;74:3107-3114'},{id:"B41",body:'Gross RJ, Rowe B. Escherichia coli diarrhoea. The Journal of Hygiene. 1985;95:531-550'},{id:"B42",body:'Mendez Arancibia E, Pitart C, Ruiz J, Marco F, Gascon J, et al. Evolution of antimicrobial resistance in enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli causing traveller’s diarrhoea. The Journal of Antimicrobial Chemotherapy. 2009;64:343-347'},{id:"B43",body:'von Mentzer A, Blackwell GA, Pickard D, Boinett CJ, Joffré E, et al. Long-read-sequenced reference genomes of the seven major lineages of enterotoxigenic Escherichia coli (ETEC) circulating in modern time. Scientific Reports. 2021;11:9256'},{id:"B44",body:'Maynard C, Fairbrother JM, Bekal S, Sanschagrin F, Levesque RC, et al. Antimicrobial resistance genes in enterotoxigenic Escherichia coli O149:K91 isolates obtained over a 23-year period from pigs. Antimicrobial Agents and Chemotherapy. 2003;47:3214-3221'},{id:"B45",body:'Steinsland H, Valentiner-Branth P, Aaby P, Mølbak K, Sommerfelt H. Clonal relatedness of enterotoxigenic Escherichia coli strains isolated from a cohort of young children in Guinea Bissau. Journal of Clinical Microbiology. 2004;42:3100-3107'},{id:"B46",body:'Steinsland H, Lacher DW, Sommerfelt H, Whittam TS. Ancestral lineages of human enterotoxigenic Escherichia coli. Journal of Clinical Microbiology. 2010;48:2916-2924'},{id:"B47",body:'Escobar-Páramo P, Clermont O, Blanc-Potard A-B, Bui H, Le Bouguénec C, et al. A specific genetic background is required for acquisition and expression of virulence factors in Escherichia coli. Molecular Biology and Evolution. 2004;21:1085-1094'},{id:"B48",body:'Turner SM, Chaudhuri RR, Jiang Z-D, DuPont H, Gyles C, et al. Phylogenetic comparisons reveal multiple acquisitions of the toxin genes by enterotoxigenic Escherichia coli strains of different evolutionary lineages. Journal of Clinical Microbiology. 2006;44:4528-4536'},{id:"B49",body:'von Mentzer A, Connor TR, Wieler LH, Semmler T, Iguchi A, et al. Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution. Nature Genetics. 2014;46:1321-1326'},{id:"B50",body:'Sahl JW, Sistrunk JR, Fraser CM, Hine E, Baby N, et al. Examination of the enterotoxigenic Escherichia coli population structure during human infection. mBio. 2015;6. Epub ahead of print July 2015. DOI: 10.1128/mBio.00501-15'},{id:"B51",body:'Sahl JW, Steinsland H, Redman JC, Angiuoli SV, Nataro JP, et al. A comparative genomic analysis of diverse clonal types of enterotoxigenic Escherichia coli reveals pathovar-specific conservation. Infection and Immunity. 2011;79:950-960'},{id:"B52",body:'Scotland SM, Smith HR, Willshaw GA, Rowe B. Vero cytotoxin production in strain of Escherichia coli is determined by genes carried on bacteriophage. The Lancet. 1983;322:216'},{id:"B53",body:'Delannoy S, Chaves BD, Ison SA, Webb HE, Beutin L, et al. Revisiting the STEC testing approach: Using espK and espV to make enterohemorrhagic Escherichia coli (EHEC) detection more reliable in beef. Frontiers in Microbiology. 2016;7. Epub ahead of print 22 January 2016. DOI: 10.3389/fmicb.2016.00001'},{id:"B54",body:'FAO, WHO. Attributing illness caused by Shiga toxin-producing Escherichia coli (STEC) to specific foods. In: Microbiological Risk Assessment. Rome, Italy: FAO; 2019. p. 74'},{id:"B55",body:'Blanco M, Blanco JE, Mora A, Rey J, Alonso JM, et al. Serotypes, virulence genes, and intimin types of shiga toxin (verotoxin)-producing Escherichia coli isolates from healthy sheep in Spain. Journal of Clinical Microbiology. 2003;41:1351-1356'},{id:"B56",body:'Hughes JM, Wilson ME, Johnson KE, Thorpe CM, Sears CL. The emerging clinical importance of non-O157 shiga toxin--producing Escherichia coli. Clinical Infectious Diseases. 2006;43:1587-1595'},{id:"B57",body:'Karama M, Mainga AO, Cenci-Goga BT, Malahlela M, El-Ashram S, et al. Molecular profiling and antimicrobial resistance of Shiga toxin-producing Escherichia coli O26, O45, O103, O121, O145 and O157 isolates from cattle on cow-calf operations in South Africa. Scientific Reports. 2019;9:11930'},{id:"B58",body:'Centers for Disease Control and Prevention (CDC). National Shiga Toxin-producing Escherichia coli (STEC) Surveillance Overview. Atlanta, Georgia, US: US Department of Health and Human Services; 2012'},{id:"B59",body:'Kim J-S, Lee M-S, Kim JH. Recent updates on outbreaks of shiga toxin-producing Escherichia coli and its potential reservoirs. Frontiers in Cellular and Infection Microbiology. 2020;10. Epub ahead of print 2020. DOI: 10.3389/fcimb.2020.00273'},{id:"B60",body:'Persad AK, LeJeune JT. Animal reservoirs of shiga toxin-producing Escherichia coli. Microbiology Spectrum. 2014;2. Epub ahead of print 15 August 2014. DOI: 10.1128/microbiolspec.EHEC-0027-2014'},{id:"B61",body:'Chekabab SM, Paquin-Veillette J, Dozois CM, Harel J. The ecological habitat and transmission of Escherichia coli O157:H7. FEMS Microbiology Letters. 2013;341:1-12'},{id:"B62",body:'Wang LYR, Jokinen CC, Laing CR, Johnson RP, Ziebell K, et al. Multi-year persistence of verotoxigenic Escherichia coli (VTEC) in a closed Canadian beef herd: A cohort study. Frontiers in Microbiology. 2018;9. Epub ahead of print 31 August 2018. DOI: 10.3389/fmicb.2018.02040'},{id:"B63",body:'Zschock M, Hamann HP, Kloppert B, Wolter W. Shiga-toxin-producing Escherichia coli in faeces of healthy dairy cows, sheep and goats: Prevalence and virulence properties. Letters in Applied Microbiology. 2000;31:203-208'},{id:"B64",body:'Melton-Celsa AR. Shiga toxin (Stx) classification, structure, and function. Microbiology Spectrum. 2014;2. Epub ahead of print 15 August 2014. DOI: 10.1128/microbiolspec.EHEC-0024-2013'},{id:"B65",body:'Farfan MJ, Torres AG. Molecular mechanisms that mediate colonization of shiga toxin-producing Escherichia coli strains. Infection and Immunity. 2012;80:903-913'},{id:"B66",body:'Cho S-H, Oh K-H, Kim S-H, Oh H-B, Park M-S. Distribution of virulence genes and their association of serotypes in pathogenic Escherichia coli isolates from diarrheal patients in Korea. Osong Public Health and Research Perspectives. 2010;1:29-35'},{id:"B67",body:'Makino S-I, Tobe T, Asakura H, Watarai M, Ikeda T, et al. Distribution of the secondary type III secretion system locus found in enterohemorrhagic Escherichia coli O157:H7 isolates among shiga toxin-producing E. coli strains. Journal of Clinical Microbiology. 2003;41:2341-2347'},{id:"B68",body:'Campellone K. Tails of two Tirs: Actin pedestal formation by enteropathogenic E. coli and enterohemorrhagic E. coli O157:H7. Current Opinion in Microbiology. 2003;6:82-90'},{id:"B69",body:'Yang X, Sun H, Fan R, Fu S, Zhang J, et al. Genetic diversity of the intimin gene (eae) in non-O157 Shiga toxin-producing Escherichia coli strains in China. Scientific Reports. 2020;10:3275'},{id:"B70",body:'Bibbal D, Loukiadis E, Kérourédan M, Peytavin de Garam C, Ferré F, et al. Intimin gene (eae) subtype-based real-time PCR strategy for specific detection of shiga toxin-producing Escherichia coli serotypes O157:H7, O26:H11, O103:H2, O111:H8, and O145:H28 in cattle feces. Applied and Environmental Microbiology. 2014;80:1177-1184'},{id:"B71",body:'Fierz L, Cernela N, Hauser E, Nüesch-Inderbinen M, Stephan R. Characteristics of shigatoxin-producing Escherichia coli strains isolated during 2010-2014 from human infections in Switzerland. Frontiers in Microbiology. 2017;8:1471'},{id:"B72",body:'Carroll KJ, Harvey-Vince L, Jenkins C, Mohan K, Balasegaram S. The epidemiology of Shiga toxin-producing Escherichia coli infections in the South East of England: November 2013–March 2017 and significance for clinical and public health. Journal of Medical Microbiology. 2019;68:930-939'},{id:"B73",body:'Hua Y, Bai X, Zhang J, Jernberg C, Chromek M, et al. Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden. Emerging Microbes & Infections. 2020;9:2562-2570'},{id:"B74",body:'Balière C, Rincé A, Delannoy S, Fach P, Gourmelon M. Molecular profiling of shiga toxin-producing Escherichia coli and enteropathogenic E. coli strains isolated from french coastal environments. Applied and Environmental Microbiology. 2016;82:3913-3927'},{id:"B75",body:'Paton AW, Srimanote P, Woodrow MC, Paton JC. Characterization of saa, a novel autoagglutinating adhesin produced by locus of enterocyte effacement-negative shiga-toxigenic Escherichia coli strains that are virulent for humans. Infection and Immunity. 2001;69:6999-7009'},{id:"B76",body:'Batisson I, Guimond M-P, Girard F, An H, Zhu C, et al. Characterization of the novel factor Paa involved in the early steps of the adhesion mechanism of attaching and effacing Escherichia coli. Infection and Immunity. 2003;71:4516-4525'},{id:"B77",body:'Wells TJ, Sherlock O, Rivas L, Mahajan A, Beatson SA, et al. EhaA is a novel autotransporter protein of enterohemorrhagic Escherichia coli O157:H7 that contributes to adhesion and biofilm formation. Environmental Microbiology. 2008;10:589-604'},{id:"B78",body:'Doughty S, Sloan J, Bennett-Wood V, Robertson M, Robins-Browne RM, et al. Identification of a novel fimbrial gene cluster related to long polar fimbriae in locus of enterocyte effacement-negative strains of enterohemorrhagic Escherichia coli. Infection and Immunity. 2002;70:6761-6769'},{id:"B79",body:'Ju W, Shen J, Toro M, Zhao S, Meng J. Distribution of pathogenicity islands OI-122, OI-43/48, and OI-57 and a high-pathogenicity island in shiga toxin-producing Escherichia coli. Applied and Environmental Microbiology. 2013;79:3406-3412'},{id:"B80",body:'EFSA BIOHAZ Panel, Koutsoumanis K, Allende A, Alvarez-Ordóñez A, Bover-Cid S, et al. Pathogenicity assessment of Shiga toxin-producing Escherichia coli (STEC) and the public health risk posed by contamination of food with STEC. EFSA Journal. 2020;18. Epub ahead of print January 2020. DOI: 10.2903/j.efsa.2020.5967'},{id:"B81",body:'Fuller CA, Pellino CA, Flagler MJ, Strasser JE, Weiss AA. Shiga toxin subtypes display dramatic differences in potency. Infection and Immunity. 2011;79:1329-1337'},{id:"B82",body:'Pradel N, Livrelli V, De Champs C, Palcoux J, Reynaud A, Cheutz F, et al. Prevalence and characterization of shiga toxin-producing Escherichia coli isolated from cattle, food, and children during a one-year prospective study in France. Journal of Clinical Microbiology. 2000;38(3):1023-1031'},{id:"B83",body:'Meng Q, Bai X, Zhao A, Lan R, Du H, et al. Characterization of Shiga toxin-producing Escherichia coli isolated from healthy pigs in China. BMC Microbiology. 2014;14:5'},{id:"B84",body:'Brett KN, Ramachandran V, Hornitzky MA, Bettelheim KA, Walker MJ, et al. stx1c is the most common shiga toxin 1 subtype among shiga toxin-producing Escherichia coli isolates from sheep but not among isolates from Cattle. Journal of Clinical Microbiology. 2003;41:926-936'},{id:"B85",body:'Byrne L, Adams N, Jenkins C. Association between Shiga toxin–producing Escherichia coli O157:H7 stx gene subtype and disease severity, England, 2009-2019. Emerging Infectious Diseases. 2020;26:2394-2400'},{id:"B86",body:'Jiang C, An T, Wang S, Wang G, Si W, et al. Role of the ehxA gene from Escherichia coli serotype O82 in hemolysis, biofilm formation, and in vivo virulence. Canadian Journal of Microbiology. 2015;61:335-341'},{id:"B87",body:'Schmidt H, Beutin L, Karch H. Molecular analysis of the plasmid-encoded hemolysin of Escherichia coli O157:H7 strain EDL 933. Infection and Immunity. 1995;63:1055-1061'},{id:"B88",body:'Tatsuno I, Horie M, Abe H, Miki T, Makino K, et al. toxB gene on pO157 of enterohemorrhagic Escherichia coli O157:H7 is required for full epithelial cell adherence phenotype. Infection and Immunity. 2001;69:6660-6669'},{id:"B89",body:'Brunder W, Schmidt H, Karch H. KatP, a novel catalase-peroxidase encoded by the large plasmid of enterohaemorrhagic Escherichia coli O157:H7. Microbiology. 1996;1996(142):3305-3315'},{id:"B90",body:'Mir RA, Kudva IT. Antibiotic-resistant Shiga toxin-producing Escherichia coli: An overview of prevalence and intervention strategies. Zoonoses and Public Health. 2019;66:1-13'},{id:"B91",body:'Pan Y, Hu B, Bai X, Yang X, Cao L, et al. Antimicrobial resistance of non-O157 shiga toxin-producing Escherichia coli isolated from humans and domestic animals. Antibiotics. 2021;10:74'},{id:"B92",body:'Schroeder CM, Zhao C, DebRoy C, Torcolini J, Zhao S, et al. Antimicrobial resistance of Escherichia coli O157 isolated from humans, cattle, swine, and food. Applied and Environmental Microbiology. 2002;68:576-581'},{id:"B93",body:'Galarce N, Sánchez F, Fuenzalida V, Ramos R, Escobar B, et al. Phenotypic and genotypic antimicrobial resistance in non-O157 Shiga toxin-producing Escherichia coli isolated from cattle and swine in Chile. Frontiers in Veterinary Science. 2020;7:367'},{id:"B94",body:'Bai X, Zhang J, Hua Y, Jernberg C, Xiong Y, et al. Genomic insights into clinical Shiga toxin-producing Escherichia coli strains: A 15-year period survey in Jönköping, Sweden. Frontiers in Microbiology. 2021;12:627861'},{id:"B95",body:'Ogura Y, Ooka T, Iguchi A, Toh H, Asadulghani M, et al. Comparative genomics reveal the mechanism of the parallel evolution of O157 and non-O157 enterohemorrhagic Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America. 2009. Epub ahead of print 5 October 2009. DOI: 10.1073/pnas.0903585106'},{id:"B96",body:'Coura FM, de Araújo DS, Mussi JMS, Silva MX, Lage AP, et al. Characterization of virulence factors and phylogenetic group determination of Escherichia coli isolated from diarrheic and non-diarrheic calves from Brazil. Folia Microbiologia (Praha). 2017;62:139-144'},{id:"B97",body:'Dallman TJ, Ashton PM, Byrne L, Perry NT, Petrovska L, et al. Applying phylogenomics to understand the emergence of Shiga-toxin-producing Escherichia coli O157:H7 strains causing severe human disease in the UK. Microbial Genomics. 2015;1:e000029'},{id:"B98",body:'Ingle DJ, Gonçalves da Silva A, Valcanis M, Ballard SA, Seemann T, et al. Emergence and divergence of major lineages of Shiga-toxin-producing Escherichia coli in Australia. Microbial Genomics. 2019;5:e000268'},{id:"B99",body:'Yang Z, Kovar J, Kim J, Nietfeldt J, Smith DR, et al. Identification of common subpopulations of non-sorbitol-fermenting, β-glucuronidase-negative Escherichia coli O157:H7 from bovine production environments and human clinical samples. Applied and Environmental Microbiology. 2004;70:6846-6854'},{id:"B100",body:'Cowley LA, Dallman TJ, Jenkins C, Sheppard SK. Phage predation shapes the population structure of shiga-toxigenic Escherichia coli O157:H7 in the UK: An evolutionary perspective. Frontiers in Genetics. 2019;0. Epub ahead of print 2019. DOI: 10.3389/fgene.2019.00763'},{id:"B101",body:'Franz E, Rotariu O, Lopes BS, MacRae M, Bono JL, et al. Phylogeographic analysis reveals multiple international transmission events have driven the global emergence of Escherichia coli O157:H7. Clinical Infectious Diseases. 2019;69:428-437'},{id:"B102",body:'Valilis E, Ramsey A, Sidiq S, DuPont HL. Non-O157 Shiga toxin-producing Escherichia coli—A poorly appreciated enteric pathogen: Systematic review. International Journal of Infectious Diseases. 2018;76:82-87'},{id:"B103",body:'Blankenship HM, Mosci RE, Dietrich S, Burgess E, Wholehan J, et al. Population structure and genetic diversity of non-O157 Shiga toxin-producing Escherichia coli (STEC) clinical isolates from Michigan. Scientific Reports. 2021;11:4461'},{id:"B104",body:'Hazen TH, Donnenberg MS, Panchalingam S, Antonio M, Hossain A, et al. Genomic diversity of EPEC associated with clinical presentations of differing severity. Nature Microbiology. 2016;1:1-9'},{id:"B105",body:'Wardlaw T, Salama P, Brocklehurst C, Chopra M, Mason E. Diarrhoea: Why children are still dying and what can be done. The Lancet. 2010;375:870-872'},{id:"B106",body:'Goosney DL, Gruenheid S, Finlay BB. Gut feelings: Enteropathogenic E. coli (EPEC) interactions with the host. Annual Review of Cell and Developmental Biology. 2000;16:173-189'},{id:"B107",body:'Mare AD, Ciurea CN, Man A, Tudor B, Moldovan V, et al. Enteropathogenic Escherichia coli—A summary of the literature. Gastroenterology Insights. 2021;12:28-40'},{id:"B108",body:'Monaghan Á, Byrne B, Fanning S, Sweeney T, McDowell D, et al. Serotypes and virulence profiles of atypical enteropathogenic Escherichia coli (EPEC) isolated from bovine farms and abattoirs. Journal of Applied Microbiology. 2013;114:595-603'},{id:"B109",body:'Scaletsky ICA. Enteropathogenic Escherichia coli. London, The United Kingdom: IntechOpen. Epub ahead of print 18 September 2019. DOI: 10.5772/intechopen.82861'},{id:"B110",body:'Elliott SJ, Sperandio V, Girón JA, Shin S, Mellies JL, et al. The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli. Infection and Immunity. 2000;68:6115-6126'},{id:"B111",body:'Trabulsi LR, Keller R, Gomes TAT. Typical and atypical enteropathogenic Escherichia coli. Emerging Infectious Diseases. 2002;8:508-513. DOI: 10.321/eid0805'},{id:"B112",body:'Hu J, Torres AG. Enteropathogenic Escherichia coli: Foe or innocent bystander? | Elsevier Enhanced Reader. Clinical Microbiology and Infection. 2015;21:729-734'},{id:"B113",body:'Zhou Z, Li X, Liu B, Beutin L, Xu J, et al. Derivation of Escherichia coli O157:H7 from Its O55:H7 precursor. PLoS One. 2010;5:e8700'},{id:"B114",body:'Moura RA, Sircili MP, Leomil L, Matté MH, Trabulsi LR, et al. Clonal relationship among atypical enteropathogenic Escherichia coli strains isolated from different animal species and humans. Applied and Environmental Microbiology. 2009;75:7399-7408'},{id:"B115",body:'Donnenberg MS. Interactions between enteropathogenic Escherichia coli and epithelial cells. Clinical Infectious Diseases. 1999;28:451-455'},{id:"B116",body:'Khursigara C, Abul-Milh M, Lau B, Girón JA, Lingwood CA, et al. Enteropathogenic Escherichia coli virulence factor bundle-forming pilus has a binding specificity for phosphatidylethanolamine. Infection and Immunity. 2001;69:6573-6579'},{id:"B117",body:'Afset JE, Bruant G, Brousseau R, Harel J, Anderssen E, et al. Identification of virulence genes linked with diarrhea due to atypical enteropathogenic Escherichia coli by DNA microarray analysis and PCR. Journal of Clinical Microbiology. 2006;44:3703-3711'},{id:"B118",body:'Clarke SC, Haigh RD, Freestone PPE, Williams PH. Virulence of enteropathogenic Escherichia coli, a global pathogen. Clinical Microbiology Reviews. 2003;16:365-378'},{id:"B119",body:'Lara-Ochoa C, González-Lara F, Romero-González LE, Jaramillo-Rodríguez JB, Vázquez-Arellano SI, et al. The transcriptional activator of the bfp operon in EPEC (PerA) interacts with the RNA polymerase alpha subunit. Scientific Reports. 2021;11:8541'},{id:"B120",body:'Tobe T, Sasakawa C. Role of bundle-forming pilus of enteropathogenic Escherichia coli in host cell adherence and in microcolony development. Cellular Microbiology. 2001;3:579-585'},{id:"B121",body:'Morabito S, Tozzoli R, Oswald E, Caprioli A. A mosaic pathogenicity island made up of the locus of enterocyte effacement and a pathogenicity island of Escherichia coli O157:H7 is frequently present in attaching and effacing E. coli. Infection and Immunity. 2003;71:3343-3348'},{id:"B122",body:'Dulguer MV, Fabbricotti SH, Bando SY, Moreira-Filho CA, Fagundes-Neto U, et al. Atypical enteropathogenic Escherichia coli strains: Phenotypic and genetic profiling reveals a strong association between enteroaggregative E. coli heat-stable enterotoxin and diarrhea. The Journal of Infectious Diseases. 2003;188:1685-1694'},{id:"B123",body:'Silva LE, Souza TB, Silva NP, Scaletsky IC. Detection and genetic analysis of the enteroaggregative Escherichia coli heat-stable enterotoxin (EAST1) gene in clinical isolates of enteropathogenic Escherichia coli (EPEC) strains. BMC Microbiology. 2014;14:135'},{id:"B124",body:'DuPont HL. Persistent diarrhea: A clinical review. JAMA. 2016;315:2712'},{id:"B125",body:'Karami P, Bazmamoun H, Sedighi I, Mozaffari Nejad AS, Aslani MM, et al. Antibacterial resistance patterns of extended spectrum β-lactamase—producing enteropathogenic Escherichia coli strains isolated from children. Arab Journal of Gastroenterology. 2017;18:206-209'},{id:"B126",body:'Sirous M, Hashemzadeh M, Keshtvarz M, Amin M, Shams N, et al. Molecular characterization and antimicrobial resistance of enteropathogenic Escherichia coli in children from Ahvaz, Iran. Jundishapur Journal of Microbiology. 2020;13. Epub ahead of print 28 September 2020. DOI: 10.5812/jjm.100877'},{id:"B127",body:'Scaletsky IC, Souza TB, Aranda KR, Okeke IN. Genetic elements associated with antimicrobial resistance in enteropathogenic Escherichia coli (EPEC) from Brazil. BMC Microbiology. 2010;10:25'},{id:"B128",body:'Ingle DJ, Levine MM, Kotloff KL, Holt KE, Robins-Browne RM. Dynamics of antimicrobial resistance in intestinal Escherichia coli from children in community settings in South Asia and sub-Saharan Africa. Nature Microbiology. 2018;3:1063-1073'},{id:"B129",body:'Lacher DW, Steinsland H, Blank ET, Donnenberg MS, Whittman TS. Molecular evolution of typical enteropathogenic Escherichia coli: Clonal analysis by multilocus sequence typing and virulence gene allelic profiling. Journal of Bacteriology. 2007;189:342-350'},{id:"B130",body:'Hazen TH, Sahl JW, Fraser CM, Donnenberg MS, Scheutz F, et al. Refining the pathovar paradigm via phylogenomics of the attaching and effacing Escherichia coli. Proceedings of the National Academy of Sciences. 2013;110:12810-12815'},{id:"B131",body:'Beutin L, Orskov I, Orskov F, Zimmermann S, Prada J, et al. Clonal diversity and virulence factors in strains of Escherichia coli of the classic enteropathogenic serogroup 0114. The Journal of Infectious Diseases. 1990;162:1329-1334'},{id:"B132",body:'Hernandes RT, Hazen TH, dos Santos LF, Richter TKS, Michalski JM, et al. Comparative genomic analysis provides insight into the phylogeny and virulence of atypical enteropathogenic Escherichia coli strains from Brazil. PLoS Neglected Tropical Diseases. 2020;14:e0008373'},{id:"B133",body:'Ingle DJ, Tauschek M, Edwards DJ, Hocking DM, Pickard DJ, et al. Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants. Nature Microbiology. 2016;1:1-9'},{id:"B134",body:'Okeke IN, Nataro JP. Enteroaggregative Escherichia coli. The Lancet. Infectious Diseases. 2001;1:10'},{id:"B135",body:'Sobieszczanska BM, Osek J, Wasko-Czopnik D, Dworniczek E, Jermakow K. Association of enteroaggregative Escherichia coli with irritable bowel syndrome | Elsevier Enhanced Reader. Clinical Microbiology and Infection. 2007;13:404-407'},{id:"B136",body:'Huang DB, Mohanty A, DuPont HL, Okhuysen PC, Chiang T. A review of an emerging enteric pathogen: Enteroaggregative Escherichia coli. Journal of Medical Microbiology. 2006;2006(55):1303-1311'},{id:"B137",body:'Estrada-Garcia T, Perez-Martinez I, Bernal-Reynaga R, Zaidi MB. Enteroaggregative Escherichia coli: A pathogen bridging the north and south. Current Tropical Medicine Reports. 2014;1(2):88-96. Epub ahead of print 25 March 2014. DOI: 10.1007/s40475-014-0018-7'},{id:"B138",body:'Kaur P, Chakraborti A, Asea A. Enteroaggregative Escherichia coli: An emerging enteric food borne pathogen. Interdisciplinary Perspectives on Infectious Diseases. 2010;2010:e254159'},{id:"B139",body:'Huppertz H-I, Rutkowski S, Aleksic S, Karch H. Acute and chronic diarrhoea and abdominal colic associated with enteroaggregative Escherichia coli in young children living in western Europe. The Lancet. 1997;349:1660-1662'},{id:"B140",body:'Jenkins C, Chart H, Willshaw GA, Cheasty T, Smith HR. Genotyping of enteroaggregative Escherichia coli and identification of target genes for the detection of both typical and atypical strains. Diagnostic Microbiology and Infectious Disease. 2006;55:13-19'},{id:"B141",body:'Kimata K, Lee K, Watahiki M, Isobe J, Ohnishi M, et al. Global distribution of epidemic-related Shiga toxin 2 encoding phages among enteroaggregative Escherichia coli. Scientific Reports. 2020;10:11738'},{id:"B142",body:'Boisen N, Melton-Celsa AR, Scheutz F, O’Brien AD, Nataro JP. Shiga toxin 2a and Enteroaggregative Escherichia coli—A deadly combination. Gut Microbes. 2015;6:272-278'},{id:"B143",body:'Jonsson R, Struve C, Boisen N, Mateiu RV, Santiago AE, et al. Novel aggregative adherence fimbria variant of enteroaggregative Escherichia coli. Infection and Immunity. 2015;83:1396-1405'},{id:"B144",body:'Dias RCB, Tanabe RHS, Vieira MA, Cergole-Novella MC, dos Santos LF, et al. Analysis of the virulence profile and phenotypic features of typical and atypical enteroaggregative Escherichia coli (EAEC) isolated from diarrheal patients in Brazil. Frontiers in Cellular and Infection Microbiology. 2020;0. Epub ahead of print 2020. DOI: 10.3389/fcimb.2020.00144'},{id:"B145",body:'Henderson IR, Czeczulin J, Eslava C, Noriega F, Nataro JP. Characterization of pic, a secreted protease of Shigella flexneri and Enteroaggregative Escherichia coli. Infection and Immunity. 1999;67:5587-5596'},{id:"B146",body:'Boisen N, Østerlund MT, Joensen KG, Santiago AE, Mandomando I, et al. Redefining enteroaggregative Escherichia coli (EAEC): Genomic characterization of epidemiological EAEC strains. PLoS Neglected Tropical Diseases. 2020;14:e0008613'},{id:"B147",body:'Johnson T, Nolan LK. Pathogenomics of the virulence plasmids of Escherichia coli. Microbiology and Molecular Biology Reviews. 2009;73:750-774'},{id:"B148",body:'Mueller M, Grauschopf U, Maier T, Glockshuber R, Ban N. The structure of a cytolytic α-helical toxin pore reveals its assembly mechanism. Nature. 2009;459:726-730'},{id:"B149",body:'Andrade FB, Abreu AG, Nunes KO, Gomes TAT, Piazza RMF, et al. Distribution of serine protease autotransporters of Enterobacteriaceae in typical and atypical enteroaggregative Escherichia coli. Infection, Genetics and Evolution. 2017;50:83-86'},{id:"B150",body:'Guiral E, Gonçalves Quiles M, Muñoz L, Moreno-Morales J, Alejo-Cancho I, et al. Emergence of resistance to quinolones and β-lactam antibiotics in enteroaggregative and enterotoxigenic Escherichia coli causing traveler’s diarrhea. Antimicrobial Agents and Chemotherapy. 2019;63. Epub ahead of print February 2019. DOI: 10.1128/AAC.01745-18'},{id:"B151",body:'Ochoa TJ, Ruiz J, Molina M, del Valle LJ, O MV, et al. High frequency of antimicrobial resistance of diarrheagenic E. coli in Peruvian infants. The American Journal of Tropical Medicine and Hygiene. 2009;81:296-301'},{id:"B152",body:'Khoshvaght H, Haghi F, Zeighami H. Extended spectrum betalactamase producing Enteroaggregative Escherichia coli from young children in Iran. Gastroenterology and Hepatology from Bed to Bench. 2014;7:131-136'},{id:"B153",body:'Riveros M, Riccobono E, Durand D, Mosquito S, Ruiz J, et al. Plasmid-mediated quinolone resistance genes in enteroaggregative Escherichia coli from infants in Lima, Peru. International Journal of Antimicrobial Agents. 2012;39:540-542'},{id:"B154",body:'Herrera-León S, Llorente MT, Sánchez S. Plasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler’s diarrhea cases. Antimicrobial Agents and Chemotherapy. 2016;60:1950-1951'},{id:"B155",body:'Do Nascimento V, Day MR, Doumith M, Hopkins KL, Woodford N, et al. Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of enteroaggregative Escherichia coli isolated from cases of diarrhoeal disease in England, 2015-16. The Journal of Antimicrobial Chemotherapy. 2017;72:3288-3297'},{id:"B156",body:'Czeczulin JR, Whittam TS, Henderson IR, Navarro-Garcia F, Nataro JP. Phylogenetic analysis of enteroaggregative and diffusely adherent Escherichia coli. Infection and Immunity. 1999;67:2692-2699'},{id:"B157",body:'Okeke IN, Wallace-Gadsden F, Simons HR, Matthews N, Labar AS, et al. Multi-locus sequence typing of enteroaggregative Escherichia coli isolates from Nigerian children uncovers multiple lineages. PLoS One. 2010;5:e14093'},{id:"B158",body:'Modgil V, Mahindroo J, Narayan C, Kalia M, Yousuf M, et al. Comparative analysis of virulence determinants, phylogroups, and antibiotic susceptibility patterns of typical versus atypical Enteroaggregative E. coli in India. PLOS Neglected Tropical Diseases. 2020;14:e0008769'},{id:"B159",body:'Pasqua M, Michelacci V, Di Martino ML, Tozzoli R, Grossi M, et al. The intriguing evolutionary journey of enteroinvasive E. coli (EIEC) toward pathogenicity. Frontiers in Microbiology. 2017;8. Epub ahead of print 5 December 2017. DOI: 10.3389/fmicb.2017.02390'},{id:"B160",body:'Herzig CTA. Notes from the field: Enteroinvasive Escherichia coli outbreak associated with a Potluck Party — North Carolina, June–July 2018. Morbidity and Mortality Weekly Report is a Weekly. 2019;68. Epub ahead of print 2019. DOI: 10.15585/mmwr.mm6807a5'},{id:"B161",body:'Ewing WH, Gravatti JL. Shigella types encountered in the mediterranean area 1. Journal of Bacteriology. 1947;53:191-195'},{id:"B162",body:' Rowe B, Gross RJ, Woodroof DP. Proposal to recognise seroovar 145/46 (synonyms: 147, Shigella 13, Shigella sofia, and Shigella manolovii) as a new Escherichia coli O group, O164. International Journal of Systematic Bacteriology. 1977;27(1):15-18'},{id:"B163",body:'Escher M, Scavia G, Morabito S, Tozzoli R, Maugliani A, et al. A severe foodborne outbreak of diarrhoea linked to a canteen in Italy caused by enteroinvasive Escherichia coli, an uncommon agent. Epidemiology and Infection. 2014;142:2559-2566'},{id:"B164",body:'Newitt S, MacGregor V, Robbins V, Bayliss L, Chattaway MA, et al. Two linked enteroinvasive Escherichia coli outbreaks, Nottingham, UK, June 2014. Emerging Infectious Diseases. 2016;22:1178-1184'},{id:"B165",body:'Fung CC, Octavia S, Mooney A-M, Lan R. Virulence variations in Shigella and enteroinvasive Escherichia coli using the Caenorhabditis elegans model. FEMS Microbiology Letters. 2015;362:1-5'},{id:"B166",body:'Nataro JP, Seriwatana J, Fasano A, Maneval DR, Guers LD, et al. Identification and cloning of a novel plasmid-encoded enterotoxin of enteroinvasive Escherichia coli and Shigella strains. Infection and Immunity. 1995;63:4721-4728'},{id:"B167",body:'Farajzadeh-Sheikh A, Savari M, Ahmadi K, Nave HH, Shahin M, et al. Distribution of genes encoding virulence factors and the genetic diversity of enteroinvasive Escherichia coli (EIEC) isolates from patients with diarrhea in Ahvaz, Iran. Infection and Drug Resistance. 2020;13:119-127'},{id:"B168",body:'Hosseini Nave H, Mansouri S, Taati Moghadam M, Moradi M. Virulence gene profile and multilocus variable-number tandem-repeat analysis (MLVA) of enteroinvasive Escherichia coli (EIEC) isolates from patients with diarrhea in Kerman, Iran. Jundishapur Journal of Microbiology. 2016;9:e33529'},{id:"B169",body:'Marbou WJT, Jain P, Samajpati S, Halder G, Mukhopadhyay AK, et al. Profiling virulence and antimicrobial resistance markers of enterovirulent Escherichia coli from fecal isolates of adult patients with enteric infections in West Cameroon. Osong Public Health and Research Perspectives. 2020;11:216-230'},{id:"B170",body:'Hartman AB, Essiet II, Isenbarger DW, Lindler LE. Epidemiology of tetracycline resistance determinants in Shigella spp. and Enteroinvasive Escherichia coli: Characterization and dissemination of tet(A)-1. Journal of Clinical Microbiology. 2003;41:1023-1032'},{id:"B171",body:'Ahmed AM, Miyoshi S, Shinoda S, Shimamoto T. Molecular characterization of a multidrug-resistant strain of enteroinvasive Escherichia coli O164 isolated in Japan. Journal of Medical Microbiology. 2005;2005(54):273-278'},{id:"B172",body:'Escobar-Páramo P, Giudicelli C, Parsot C, Denamur E. The evolutionary history of Shigella and Enteroinvasive Escherichia coli revised. Journal of Molecular Evolution. 2003;57:140-148'},{id:"B173",body:'Lan R, Alles MC, Donohoe K, Martinez MB, Reeves PR. Molecular evolutionary relationships of enteroinvasive Escherichia coli and Shigella spp. Infection and Immunity. 2004;72:5080-5088'},{id:"B174",body:'Pettengill EA, Pettengill JB, Binet R. Phylogenetic analyses of Shigella and Enteroinvasive Escherichia coli for the identification of molecular epidemiological markers: Whole-genome comparative analysis does not support distinct genera designation. Frontiers in Microbiology. 2016;0. Epub ahead of print 2016. DOI: 10.3389/ fmicb.2015.01573'},{id:"B175",body:'Hazen TH, Leonard SR, Lampel KA, Lacher DW, Maurelli AT, et al. Investigating the relatedness of enteroinvasive Escherichia coli to other E. coli and Shigella isolates by using comparative genomics. Infection and Immunity. 2016;84:2362-2371'},{id:"B176",body:'Hawkey J, Monk JM, Billman-Jacobe H, Palsson B, Holt KE. Impact of insertion sequences on convergent evolution of Shigella species. PLoS Genetics. 2020;16:e1008931'},{id:"B177",body:'Servin AL. Pathogenesis of human diffusely adhering Escherichia coli expressing Afa/Dr adhesins (Afa/Dr DAEC): Current insights and future challenges. Clinical Microbiology Reviews. 2014;27:823-869'},{id:"B178",body:'Scaletsky ICA, Fabbricotti SH, Carvalho RLB, Nunes CR, Maranhão HS, et al. Diffusely adherent Escherichia coli as a cause of acute diarrhea in young children in Northeast Brazil: A case-control study. Journal of Clinical Microbiology. 2002;40:645-648'},{id:"B179",body:'Lopes LM, Fabbricotti SH, Ferreira AJP, Kato MAMF, Michalski J, et al. Heterogeneity among strains of diffusely adherent Escherichia coli isolated in Brazil. Journal of Clinical Microbiology. 2005;43:1968-1972'},{id:"B180",body:'Ochoa TJ, Rivera FP, Bernal M, Meza R, Ecker L, et al. Detection of the CS20 colonization factor antigen in diffuse-adhering Escherichia coli strains. FEMS Immunology and Medical Microbiology. 2010;60:186-189'},{id:"B181",body:'Le Bouguénec C, Servin AL. Diffusely adherent Escherichia coli strains expressing Afa/Dr adhesins (Afa/Dr DAEC): Hitherto unrecognized pathogens. FEMS Microbiology Letters. 2006;256:185-194'},{id:"B182",body:'Javadi K, Mohebi S, Motamedifar M, Hadi N. Characterization and antibiotic resistance pattern of diffusely adherent Escherichia coli (DAEC), isolated from paediatric diarrhoea in Shiraz, southern Iran. New Microbes and New Infections. 2020;38:100780'},{id:"B183",body:'Mansan-Almeida R, Pereira AL, Giugliano LG. Diffusely adherent Escherichia coli strains isolated from children and adults constitute two different populations. BMC Microbiology. 2013;13:1-14'},{id:"B184",body:'Taddei CR, Moreno ACR, Fernandes Filho A, Montemor LPG, Martinez MB. Prevalence of secreted autotransporter toxin gene among diffusely adhering Escherichia coli isolated from stools of children. FEMS Microbiology Letters. 2003;227:249-253'},{id:"B185",body:'Meza-Segura M, Estrada-Garcia T. Diffusely Adherent Escherichia coli. In: Torres AG (editor). Escherichia coli in the Americas. Cham: Springer International Publishing. pp. 125-147'},{id:"B186",body:'Li D, Shen M, Xu Y, Liu C, Wang W, et al. Virulence gene profiles and molecular genetic characteristics of diarrheagenic Escherichia coli from a hospital in western China. Gut Pathogen. 2018;10:35'},{id:"B187",body:'Spano LC, da Cunha KF, Monfardini MV, de Cássia Bergamaschi Fonseca R, Scaletsky ICA. High prevalence of diarrheagenic Escherichia coli carrying toxin-encoding genes isolated from children and adults in southeastern Brazil. BMC Infectious Diseases. 2017;17:773'},{id:"B188",body:'Meza-Segura M, Zaidi MB, Vera-Ponce de León A, Moran-Garcia N, Martinez-Romero E, et al. New insights into DAEC and EAEC pathogenesis and phylogeny. Frontiers in Cellular and Infection Microbiology. 2020;10. Epub ahead of print 2020. DOI: 10.3389/fcimb.2020.572951'},{id:"B189",body:'Denamur E, Clermont O, Bonacorsi S, Gordon D. The population genetics of pathogenic Escherichia coli. Nature Reviews. Microbiology. 2021;19:37-54'},{id:"B190",body:'Mosquito S, Pons MJ, Riveros M, Ruiz J, Ochoa TJ. Diarrheagenic Escherichia coli phylogroups are associated with antibiotic resistance and duration of diarrheal episode. Scientific World Journal. 2015;2015:e610403'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Opeyemi U. Lawal",address:null,affiliation:'
Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Ontario, Canada
'},{corresp:null,contributorFullName:"Valeria R. Parreira",address:null,affiliation:'
Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Ontario, Canada
Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Ontario, Canada
'}],corrections:null},book:{id:"10894",type:"book",title:"Escherichia coli",subtitle:null,fullTitle:"Escherichia coli",slug:null,publishedDate:null,bookSignature:"Dr. Marjanca Starčič Erjavec",coverURL:"https://cdn.intechopen.com/books/images_new/10894.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-870-5",printIsbn:"978-1-83969-869-9",pdfIsbn:"978-1-83969-871-2",isAvailableForWebshopOrdering:!0,editors:[{id:"58980",title:"Dr.",name:"Marjanca",middleName:null,surname:"Starčič Erjavec",slug:"marjanca-starcic-erjavec",fullName:"Marjanca Starčič Erjavec"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"414388",title:"Dr.",name:"Ayyappan",middleName:null,surname:"Narayanan",email:"ayyappan.n@ifpindia.org",fullName:"Ayyappan Narayanan",slug:"ayyappan-narayanan",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"77014",title:"Forest Vegetation and Dynamics Studies in India",slug:"forest-vegetation-and-dynamics-studies-in-india",abstract:"Forests across the globe have been exploited for resouces, and over the years the demand has increased, and forests are rather exploited instead of sustainable use. Focussed research on vegetation and forerst dynamics is necessary to preserve biodiversity and functioning of forests for sustanence of human life on Earth.This article emphasis that the India has a long history of traditional knowledge on forest and plants, and explorations from 17th century on forests and provided subsequent scientific approach on classification of forests. This also explains the developments of quantitative approach on the understanding of vegetation and forest diversity. Four case studies viz., Mudumalai, Sholayar, Uppangala, Kakachi permanent plots in the forests of Western Ghats has been explained in detail about their sampling methods with a note on the results of forest monitoring. In the case of deciduous forests, the population of plant species showed considerable fluctuations but basal area has been steadily increasing over time, and this is reflecting carbon sequestration. In Sholayar, a total of 25390 individuals of 106 woody species was recorded for < 1 cm diameter at breast height in the first census of the 10 ha plot in the tropical evergreen forest. In Uppangala, 1) a 27- year long investigation revealed that residual impact of logging in the evergreen forests and such forests would take more time to resemble unlogged forests in terms of composition and structure; 2) across a similar temporal scale, the unlogged plots trees < 30 cm gbh showed a more or less similar trend in mortality (an average of 0.8% year-1) and recruitment (1%). The Kakachi plot study revealed that 1) endemic species showed least change in stem density and basal area whereas widely distributed species showed greater change in both; 2) The overall recruitment of trees was 0.86 % per year and mortality 0.56% per year resulting in an annual turnover of 0.71% ; 3) majority of the gap species had high levels of recruitment and mortality resulting in a high turnover.Such studies can be used as early warning system to understand how the response of individual plants, species and forests with the climatic variability. In conclusion, the necessity of implementation of national level projects, the way forward of two such studies: 1) impact of climate change on Indian forests through Indian Council of Forestry Research and Education (ICFRE) colloborations and 2) Indian long term ecological observatorion, including the sampling protocols of such studies. 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These molecules can derive from the grape, in which the non-volatile forms are usually present as glycosylated molecules, the metabolic activities of yeast and bacteria, the chemical reactions taking place during the wine aging and storage, and the environment. The sulfur compounds include molecules positively correlated to the aromatic profile of wine, namely the volatile thiols, and are responsible for certain defects, imparting notes described as cabbage, onion, rotten egg, garlic, sulfur and rubber. Due to the low concentration of these molecules in wine, their high reactivity and the matrix complexity, the analytical methods which enable their detection and quantification represent a challenge. The solid phase microextraction (SPME) technique has been developed for sulfur compounds associated with off-flavors. The analysis of volatile thiols usually requires a derivatization followed by gas chromatography (GC)-MS or UPLC-MS methods. Besides the sulfur-containing aromas, another sulfur compound that deserves mention is the reduced glutathione (GSH) which has been widely studied due to its antioxidant properties. The analysis of GSH has been proposed using a liquid chromatography technique (HPLC or UPLC) coupled with fluorescence, MS and UV detectors.",book:{id:"6077",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",title:"Grapes and Wines",fullTitle:"Grapes and Wines - Advances in Production, Processing, Analysis and Valorization"},signatures:"Daniela Fracassetti and Ileana Vigentini",authors:[{id:"207271",title:"Dr.",name:"Daniela",middleName:null,surname:"Fracassetti",slug:"daniela-fracassetti",fullName:"Daniela Fracassetti"},{id:"220967",title:"Dr.",name:"Ileana",middleName:null,surname:"Vigentini",slug:"ileana-vigentini",fullName:"Ileana Vigentini"}]},{id:"66619",doi:"10.5772/intechopen.85692",title:"Contribution of the Microbiome as a Tool for Estimating Wine’s Fermentation Output and Authentication",slug:"contribution-of-the-microbiome-as-a-tool-for-estimating-wine-s-fermentation-output-and-authenticatio",totalDownloads:1087,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Wine is the alcoholic beverage which is the product of alcoholic fermentation, usually, of fresh grape must. Grape microbiome is the source of a vastly diverse pool of filamentous fungi, yeast, and bacteria, the combination of which plays a crucial role for the quality of the final product of any grape must fermentation. In recent times, the significance of this pool of microorganisms has been acknowledged by several studies analyzing the microbial ecology of grape berries of different geographical origins, cultural practices, grape varieties, and climatic conditions. Furthermore, the microbial evolution of must during fermentation process has been overstudied. The combination of the microbial evolution along with metabolic and sensorial characterizations of the produced wines could lead to the suggestion of the microbial terroir. These aspects are today leading to open a new horizon for products such as wines, especially in the case of PDO-PGI products. The aims of this review is to describe (a) how the microbiome communities are dynamically differentiated during the process of fermentation from grape to ready-to-drink wine, in order to finalize each wine’s unique sensorial characteristics, and (b) whether the microbiome could be used as a fingerprinting tool for geographical indication, based on high-throughput sequencing (HTS) technologies. Nowadays, it has been strongly indicated that microbiome analysis of grapes and fermenting musts using next-generation sequencing (NGS) could open a new horizon for wine, in the case of protected designation of origin (PDO) and protected geographical indication (PGI) determination.",book:{id:"8054",slug:"advances-in-grape-and-wine-biotechnology",title:"Advances in Grape and Wine Biotechnology",fullTitle:"Advances in Grape and Wine Biotechnology"},signatures:"Dimitrios A. Anagnostopoulos, Eleni Kamilari and Dimitrios Tsaltas",authors:[{id:"180885",title:"Associate Prof.",name:"Dimitris",middleName:null,surname:"Tsaltas",slug:"dimitris-tsaltas",fullName:"Dimitris Tsaltas"},{id:"203761",title:"MSc.",name:"Dimitris",middleName:null,surname:"Anagnostopoulos",slug:"dimitris-anagnostopoulos",fullName:"Dimitris Anagnostopoulos"},{id:"271801",title:"Ms.",name:"Elena",middleName:null,surname:"Kamilari",slug:"elena-kamilari",fullName:"Elena Kamilari"}]},{id:"67444",doi:"10.5772/intechopen.86443",title:"Somatic Variation and Cultivar Innovation in Grapevine",slug:"somatic-variation-and-cultivar-innovation-in-grapevine",totalDownloads:1032,totalCrossrefCites:4,totalDimensionsCites:9,abstract:"Paradoxically, continuous vegetative multiplication of traditional grapevine cultivars aimed to maintain cultivar attributes in this highly heterozygous species ends in the accumulation of considerable somatic variation. This variation has long contributed to cultivar adaptation and evolution under changing environmental and cultivation conditions and has also been a source of novel traits. Understanding how this somatic variation originates provides tools for genetics-assisted tracking of selected variants and breeding. Potentially, the identification of the mutations causing the observed phenotypic variation can now help to direct genome editing approaches to improve the genotype of elite traditional cultivars. Molecular characterization of somatic variants can also generate basic information helping to understand gene biological function. In this chapter, we review the state of the art on somatic variation in grapevine at phenotypic and genome sequence levels, present possible strategies for the study of this variation, and describe a few examples in which the genetic and molecular basis or very relevant grapevine traits were successfully identified.",book:{id:"8054",slug:"advances-in-grape-and-wine-biotechnology",title:"Advances in Grape and Wine Biotechnology",fullTitle:"Advances in Grape and Wine Biotechnology"},signatures:"Pablo Carbonell-Bejerano, Carolina Royo, Nuria Mauri, Javier Ibáñez and José Miguel Martínez Zapater",authors:[{id:"287215",title:"Prof.",name:"Jose Miguel",middleName:null,surname:"Martinez Zapater",slug:"jose-miguel-martinez-zapater",fullName:"Jose Miguel Martinez Zapater"},{id:"287226",title:"Dr.",name:"Javier",middleName:null,surname:"Ibáñez",slug:"javier-ibanez",fullName:"Javier Ibáñez"},{id:"300441",title:"Dr.",name:"Pablo",middleName:null,surname:"Carbonell-Bejerano",slug:"pablo-carbonell-bejerano",fullName:"Pablo Carbonell-Bejerano"},{id:"300442",title:"Dr.",name:"Carolina",middleName:null,surname:"Royo",slug:"carolina-royo",fullName:"Carolina Royo"},{id:"300444",title:"Dr.",name:"Nuria",middleName:null,surname:"Mauri",slug:"nuria-mauri",fullName:"Nuria Mauri"}]},{id:"59216",doi:"10.5772/intechopen.73132",title:"Potential for Use of the Residues of the Wine Industry in Human Nutrition and as Agricultural Input",slug:"potential-for-use-of-the-residues-of-the-wine-industry-in-human-nutrition-and-as-agricultural-input",totalDownloads:1253,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"The use of underutilized resources, with the aim of increasing productivity and creating wealth, will increasingly deserve the attention of the wine sector. The treatment of agricultural by-products will increasingly enter the priority agenda of the agribusiness sector, with a view to its use, the environment’s re-cleanliness and, in many cases, whenever possible, for both purposes. Solid waste from the process of grape industrialization, when not adequately disposed, is aggressive to the environment. Such residues release significant amounts of liquid effluents when disposed in the soil, and this liquid contains high content of nutrients, organic matter, and other elements that can change the environment, especially of streams and sources, causing the death of aquatic beings. However, if properly used, they can be used as raw materials for other purposes. The solid residues of industrially processed grapes, which may have some potential economic interest, are pomace, seeds, liquid (lees), and other materials. In this context, this chapter presents the description of these by-products and their potential for use.",book:{id:"6077",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",title:"Grapes and Wines",fullTitle:"Grapes and Wines - Advances in Production, Processing, Analysis and Valorization"},signatures:"Renato Vasconcelos Botelho, Gabriela Datsch Bennemann,\nYohandra Reyes Torres and Alessandro Jefferson Sato",authors:[{id:"64335",title:"Prof.",name:"Renato",middleName:"Vasconcelos",surname:"Botelho",slug:"renato-botelho",fullName:"Renato Botelho"},{id:"208714",title:"MSc.",name:"Gabriela",middleName:null,surname:"Datsch Bennemann",slug:"gabriela-datsch-bennemann",fullName:"Gabriela Datsch Bennemann"},{id:"208715",title:"Dr.",name:"Yohandra",middleName:null,surname:"Reyes Torres",slug:"yohandra-reyes-torres",fullName:"Yohandra Reyes Torres"},{id:"208716",title:"Dr.",name:"Alessandro Jefferson",middleName:null,surname:"Sato",slug:"alessandro-jefferson-sato",fullName:"Alessandro Jefferson Sato"}]}],mostDownloadedChaptersLast30Days:[{id:"58638",title:"Occurrence and Analysis of Sulfur Compounds in Wine",slug:"occurrence-and-analysis-of-sulfur-compounds-in-wine",totalDownloads:1953,totalCrossrefCites:4,totalDimensionsCites:11,abstract:"Sulfur compounds play an important role in the sensory characteristics of wine. These molecules can derive from the grape, in which the non-volatile forms are usually present as glycosylated molecules, the metabolic activities of yeast and bacteria, the chemical reactions taking place during the wine aging and storage, and the environment. The sulfur compounds include molecules positively correlated to the aromatic profile of wine, namely the volatile thiols, and are responsible for certain defects, imparting notes described as cabbage, onion, rotten egg, garlic, sulfur and rubber. Due to the low concentration of these molecules in wine, their high reactivity and the matrix complexity, the analytical methods which enable their detection and quantification represent a challenge. The solid phase microextraction (SPME) technique has been developed for sulfur compounds associated with off-flavors. The analysis of volatile thiols usually requires a derivatization followed by gas chromatography (GC)-MS or UPLC-MS methods. Besides the sulfur-containing aromas, another sulfur compound that deserves mention is the reduced glutathione (GSH) which has been widely studied due to its antioxidant properties. The analysis of GSH has been proposed using a liquid chromatography technique (HPLC or UPLC) coupled with fluorescence, MS and UV detectors.",book:{id:"6077",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",title:"Grapes and Wines",fullTitle:"Grapes and Wines - Advances in Production, Processing, Analysis and Valorization"},signatures:"Daniela Fracassetti and Ileana Vigentini",authors:[{id:"207271",title:"Dr.",name:"Daniela",middleName:null,surname:"Fracassetti",slug:"daniela-fracassetti",fullName:"Daniela Fracassetti"},{id:"220967",title:"Dr.",name:"Ileana",middleName:null,surname:"Vigentini",slug:"ileana-vigentini",fullName:"Ileana Vigentini"}]},{id:"57497",title:"Recovering Ancient Grapevine Varieties: From Genetic Variability to In Vitro Conservation, A Case Study",slug:"recovering-ancient-grapevine-varieties-from-genetic-variability-to-in-vitro-conservation-a-case-stud",totalDownloads:1767,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"A great number of varieties have been described in grapevine; however, few of them are currently in use. The increasing concern on varietal diversity loss has encouraged actions for recovering and preserving grapevine germplasm, which represents valuable resources for breeding as well as for diversification in grapevine-derived products. On the other hand, it is expected that this important crop, which is distributed in warm areas worldwide, will suffer the climate changes. Therefore, it is also convenient the identification of intravarietal variability and the recovery of accessions well adapted to particular environments. In this chapter, we will contribute to highlight the importance of recovering ancient materials, the usefulness of SSR markers to determine their molecular profile, the importance to analyze their virus status, and the possibilities that offer biotechnological tools for virus sanitation and in vitro storage as a complement of field preservation. In this context, we have evaluated different grapevine accessions and developed in vitro culture protocols for micropropagation, sanitation, and storage grapevine cultivars. In this work, we report the results obtained for the historic variety “Valencí Blanc” (or “Beba”) and the historic and endangered variety “Esclafagerres” (“Esclafacherres” or “Esclafacherris”).",book:{id:"6077",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",title:"Grapes and Wines",fullTitle:"Grapes and Wines - Advances in Production, Processing, Analysis and Valorization"},signatures:"Carmina Gisbert, Rosa Peiró, Tania San Pedro, Antonio Olmos,\nCarles Jiménez and Julio García",authors:[{id:"207745",title:"Dr.",name:"Carmina",middleName:null,surname:"Gisbert",slug:"carmina-gisbert",fullName:"Carmina Gisbert"},{id:"207748",title:"Dr.",name:"Rosa María",middleName:null,surname:"Peiró",slug:"rosa-maria-peiro",fullName:"Rosa María Peiró"},{id:"207749",title:"Ms.",name:"Tania",middleName:null,surname:"San Pedro Galán",slug:"tania-san-pedro-galan",fullName:"Tania San Pedro Galán"},{id:"207750",title:"Dr.",name:"Antonio",middleName:null,surname:"Olmos",slug:"antonio-olmos",fullName:"Antonio Olmos"}]},{id:"58633",title:"The Evolution of Polyphenols from Grapes to Wines",slug:"the-evolution-of-polyphenols-from-grapes-to-wines",totalDownloads:2021,totalCrossrefCites:5,totalDimensionsCites:13,abstract:"Polyphenols play an important role in the quality of wines, due to their contribution to the wine sensory properties: color, astringency and bitterness. They act as antioxidants, having positive role in human health. They can be divided into non-flavonoid (hydroxybenzoic and hydroxycinnamic acids and stilbenes) and flavonoid compounds (anthocyanins, flavan-3-ols and flavonols). Anthocyanins are responsible for the color of red grapes and wines, hydroxycinnamic and hydroxybenzoic acids act as copigments, stilbenes as antioxidants and the flavan-3-ols are mainly responsible for the astringency, bitterness and structure of wines, being involved also in the color stabilization during aging. This chapter will focus on the chemical structures of the main polyphenols, their identification and quantification in grapes and wines by advanced analytical techniques, highlighting also the maceration and aging impact on the polyphenols evolution. The factors influencing the phenolic accumulation in grapes are also reviewed, emphasizing as well the relationship between phenolic content in grapes versus wine. Polyphenolic changes during the wine making process are highlighted along with the main polyphenol extraction methods and analysis techniques. This research will contribute to the improvement in the knowledge of polyphenols: their presence in grapes, the relationship with wine quality and the influence of the external factors on their evolution.",book:{id:"6077",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",title:"Grapes and Wines",fullTitle:"Grapes and Wines - Advances in Production, Processing, Analysis and Valorization"},signatures:"Violeta-Carolina Niculescu, Nadia Paun and Roxana-Elena Ionete",authors:[{id:"187102",title:"Dr.",name:"Roxana",middleName:null,surname:"Ionete",slug:"roxana-ionete",fullName:"Roxana Ionete"},{id:"206056",title:"Dr.",name:"Violeta",middleName:"Carolina",surname:"Niculescu",slug:"violeta-niculescu",fullName:"Violeta Niculescu"},{id:"207020",title:"Mrs.",name:"Nadia",middleName:null,surname:"Paun",slug:"nadia-paun",fullName:"Nadia Paun"}]},{id:"67760",title:"Production and Marketing of Low-Alcohol Wine",slug:"production-and-marketing-of-low-alcohol-wine",totalDownloads:1299,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Moderate wine consumption may be associated with specific health benefits and a healthy lifestyle. However, increased amounts of ethanol are cytotoxic and associated with adverse health outcomes. Alcohol reduction in wine might be an avenue to reduce alcohol related harm without forcing consumers to compromise on lifestyle and benefit from positive aspects of moderate consumption. The aim of this review is to give an overview of viticultural and pre and post fermentation methods to produce low-alcohol wine, and to summarize the current evidence on the consumer acceptance and behaviour related to low-alcohol wine. Strategies for the labelling and marketing of wines with reduced alcohol content are discussed.",book:{id:"8054",slug:"advances-in-grape-and-wine-biotechnology",title:"Advances in Grape and Wine Biotechnology",fullTitle:"Advances in Grape and Wine Biotechnology"},signatures:"Tamara Bucher, Kristine Deroover and Creina Stockley",authors:[{id:"289140",title:"Dr.",name:"Creina",middleName:null,surname:"Stockley",slug:"creina-stockley",fullName:"Creina Stockley"},{id:"289141",title:"Dr.",name:"Tamara",middleName:null,surname:"Bucher",slug:"tamara-bucher",fullName:"Tamara Bucher"},{id:"289142",title:"Ms.",name:"Kristine",middleName:null,surname:"Deroover",slug:"kristine-deroover",fullName:"Kristine Deroover"}]},{id:"57946",title:"Microbiological, Physical, and Chemical Procedures to Elaborate High-Quality SO2-Free Wines",slug:"microbiological-physical-and-chemical-procedures-to-elaborate-high-quality-so2-free-wines",totalDownloads:1613,totalCrossrefCites:5,totalDimensionsCites:8,abstract:"Sulfur dioxide (SO2) is the most preservative used in the wine industry and has been widely applied, as antioxidant and antibacterial agent. However, the use of sulfur dioxide implicates a range of adverse clinical effects. Therefore, the replacement of the SO2 content in wines is one of the most important challenges for scientist and winemakers. This book chapter gives an overview regarding different microbiological, physical, and chemical alternatives to elaborate high-quality SO2-free wines. In the present chapter, original research articles as well as review articles and results obtained by the research group of the Wine Technology Center (VITEC) are shown. This study provides useful information related to this novel and healthy type of wines, highlighting the development of winemaking strategies and procedures.",book:{id:"6077",slug:"grapes-and-wines-advances-in-production-processing-analysis-and-valorization",title:"Grapes and Wines",fullTitle:"Grapes and Wines - Advances in Production, Processing, Analysis and Valorization"},signatures:"Raúl Ferrer-Gallego, Miquel Puxeu, Laura Martín, Enric Nart, Claudio\nHidalgo and Imma Andorrà",authors:[{id:"207221",title:"Dr.",name:"Raúl",middleName:null,surname:"Ferrer-Gallego",slug:"raul-ferrer-gallego",fullName:"Raúl Ferrer-Gallego"},{id:"208597",title:"Dr.",name:"Miquel",middleName:null,surname:"Puxeu",slug:"miquel-puxeu",fullName:"Miquel Puxeu"},{id:"208598",title:"Dr.",name:"Laura",middleName:null,surname:"Martín",slug:"laura-martin",fullName:"Laura Martín"},{id:"208599",title:"Mr.",name:"Enric",middleName:null,surname:"Nart",slug:"enric-nart",fullName:"Enric Nart"},{id:"208600",title:"Dr.",name:"Claudio",middleName:null,surname:"Hidalgo",slug:"claudio-hidalgo",fullName:"Claudio Hidalgo"},{id:"208601",title:"Dr.",name:"Imma",middleName:null,surname:"Andorrà",slug:"imma-andorra",fullName:"Imma Andorrà"}]}],onlineFirstChaptersFilter:{topicId:"1410",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81659",title:"State-of-the-Art Knowledge about 2,4,6-Trichloroanisole (TCA) and Strategies to Avoid Cork Taint in Wine",slug:"state-of-the-art-knowledge-about-2-4-6-trichloroanisole-tca-and-strategies-to-avoid-cork-taint-in-wi",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.103709",abstract:"Cork stoppers have been used for many centuries to seal wine in various vessels. Therefore, corks have become a traditional part of wine packaging in many countries and still play an important role for the entire wine industry. Nowadays, there is a wide option of bottle cork stoppers on the market, such as natural corks, agglomerated and technical stoppers (1 + 1), etc. These cork closures have a number of advantages, including positive sustainable and ecological aspects. Natural cork material can also be responsible for cork taint, which imparts musty/moldy or wet cardboard off-odors to the wine. However, corks are not the only source of cork taint in wine, as will be shown in the present chapter. Over the past decades, a number of compounds have been detected that can contribute to the cork taint. Among them, haloanisoles play a major role, in particular 2,4,6-trichloroanisole (TCA), which has been shown to be responsible for 50–80% or more of musty defect cases in wine. Currently, the cork and wine industries have developed a number of tools and technologies to effectively prevent cork tait in wine or to remove it if the wine is already contaminated. These practical as well as analytical questions about the TCA defects are the subject of the actual chapter.",book:{id:"10901",title:"Grapes and Wine",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg"},signatures:"Andrii Tarasov, Miguel Cabral, Christophe Loisel, Paulo Lopes, Christoph Schuessler and Rainer Jung"},{id:"78620",title:"Table Grapes: There Is More to Vitiviniculture than Wine…",slug:"table-grapes-there-is-more-to-vitiviniculture-than-wine",totalDownloads:138,totalDimensionsCites:0,doi:"10.5772/intechopen.99986",abstract:"Table grapes are fruits intended for fresh human consumption due to their sensory attributes and nutritional value. The objective of this chapter is to review the existing knowledge about table grapes, including a description of different varieties, with particular emphasis on the new highly appreciated seedless varieties. Following an introductory note on the world distribution and production of table grapes, also considering the impact of climate change, selected varieties of table grapes will be characterized in terms of their physiology, postharvest features, and consumer preferences. A morphological description of each variety, with emphasis on grape skin, grape rachis and grape cluster will be included. A final note on the drying of table grapes into raisins, and the most appropriate varieties for drying, will be given. The major changes occurring throughout the growth, development, and ripening phases of table grapes production will be discussed, regarding both physical (skin color and skin and pulp texture) and chemical (phenolic compounds, sugar content and acidity) parameters, as well as growth regulators.",book:{id:"10901",title:"Grapes and Wine",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg"},signatures:"Ana Cristina Agulheiro-Santos, Marta Laranjo and Sara Ricardo-Rodrigues"},{id:"79500",title:"New Insights about the Influence of Yeasts Autolysis on Sparkling Wines Composition and Quality",slug:"new-insights-about-the-influence-of-yeasts-autolysis-on-sparkling-wines-composition-and-quality",totalDownloads:92,totalDimensionsCites:0,doi:"10.5772/intechopen.101314",abstract:"Sparkling wines elaborated using the traditional method undergo a second fermentation in the bottle. This process involves an aging time in contact with the lees, which enriches the wine in various substances, especially proteins, mannoproteins and polysaccharides, thanks to the autolysis of the yeasts. As a result of this yeast autolysis, sparkling wines benefit from better integration of carbon dioxide and a clear sensory improvement, especially in the case of long aging. This chapter synthetizes the main results that our research group has obtained about the influence of yeasts autolysis on sparkling wines composition and quality during last years, making special emphasis on the capacity of the lees to release proteins and polysaccharides as well as on their capacity to consume oxygen and thus protect the sparkling wines from oxidation.",book:{id:"10901",title:"Grapes and Wine",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg"},signatures:"Pere Pons-Mercadé, Pol Giménez, Glòria Vilomara, Marta Conde, Antoni Cantos, Nicolas Rozès, Sergi Ferrer, Joan Miquel Canals and Fernando Zamora"},{id:"79110",title:"Microbial Decontamination by Pulsed Electric Fields (PEF) in Winemaking",slug:"microbial-decontamination-by-pulsed-electric-fields-pef-in-winemaking",totalDownloads:80,totalDimensionsCites:0,doi:"10.5772/intechopen.101112",abstract:"Pulsed Electric Fields (PEF) is a non-thermal technique that causes electroporation of cell membranes by applying very short pulses (μs) of a high-intensity electric field (kV/cm). Irreversible electroporation leads to the formation of permanent conductive channels in the cytoplasmic membrane of cells, resulting in the loss of cell viability. This effect is achieved with low energy requirements and minimal deterioration of quality. This chapter reviews the studies hitherto conducted to evaluate the potential of PEF as a technology for microbial decontamination in the winemaking process for reducing or replacing the use of SO2, for guaranteeing reproducible fermentations or for wine stabilization.",book:{id:"10901",title:"Grapes and Wine",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg"},signatures:"Carlota Delso, Alejandro Berzosa, Jorge Sanz, Ignacio Álvarez and Javier Raso"},{id:"78993",title:"pH Control and Aroma Improvement Using the Non-Saccharomyces Lachancea thermotolerans and Hanseniaspora spp. Yeasts to Improve Wine Freshness in Warm Areas",slug:"ph-control-and-aroma-improvement-using-the-non-saccharomyces-lachancea-thermotolerans-and-hanseniasp",totalDownloads:89,totalDimensionsCites:0,doi:"10.5772/intechopen.100538",abstract:"Lachancea thermotolerans is a yeast species that works as a powerful bio tool capable of metabolizing grape sugars into lactic acid via lactate dehydrogenase enzymes. The enological impact is an increase in total acidity and a decrease in pH levels (sometimes >0.5 pH units) with a concomitant slight reduction in alcohol (0.2–0.4% vol.), which helps balance freshness in wines from warm areas. In addition, higher levels of molecular SO2 are favored, which helps to decrease SO2 total content and achieve better antioxidant and antimicrobial performance. The simultaneous use with some apiculate yeast species of the genus Hanseniaspora helps to improve the aromatic profile through the production of acetyl esters and, in some cases, terpenes, which makes the wine aroma more complex, enhancing floral and fruity scents and making more complex and fresh wines. Furthermore, many species of Hanseniaspora increase the structure of wines, thus improving their body and palatability. Ternary fermentations with Lachancea thermotolerans and Hanseniaspora spp. sequentially followed by Saccharomyces cerevisiae are a useful bio tool for producing fresher wines from neutral varieties in warm areas.",book:{id:"10901",title:"Grapes and Wine",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg"},signatures:"Antonio Morata, Carlos Escott, Iris Loira, Juan Manuel Del Fresno, Cristian Vaquero, María Antonia Bañuelos, Felipe Palomero, Carmen López and Carmen González"},{id:"78970",title:"Alternatives to CU Applications in Viticulture. How R&D Projects Can Provide Applied Solutions, Helping to Establish Legislation Limits",slug:"alternatives-to-cu-applications-in-viticulture-how-r-d-projects-can-provide-applied-solutions-helpin",totalDownloads:175,totalDimensionsCites:2,doi:"10.5772/intechopen.100500",abstract:"Copper (Cu) and its based preparations have been used for over 200 years to control fungi and bacterial diseases in cultivated plants. Downy mildew caused by the obligate biotrophic oomycete Plasmopara viticola is one of the most relevant and recurrent diseases of grapevines. Recently, the use of Cu is being limited by some regulations because of its high impact at different levels (health and environmental problems). Due to its accumulation in soil, this metal causes a little controversy with the principles of sustainable production. Therefore, international legislation and initiatives have recently been arisen to start limiting its use, with the main goal to replace it. In this framework, some alternatives have been tested and others are recently being developed to replace, at least partially, the use of Cu in viticulture. Many of them, are being developed and tested under the scope of research and development EU funded projects. To not compromise sustainability targets in viticulture, results from these R&D projects need to be considered to assess the present risks of using Cu in viticulture and to better support establishing limits for its applications, considering soils vulnerability, while no sustainable alternatives are available in the market.",book:{id:"10901",title:"Grapes and Wine",coverURL:"https://cdn.intechopen.com/books/images_new/10901.jpg"},signatures:"Mario De La Fuente, David Fernández-Calviño, Bartosz Tylkowski, Josep M. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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