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Introductory Chapter: The Versatile Escherichia coli

Written By

Marjanca Starčič Erjavec

Published: 18 September 2019

DOI: 10.5772/intechopen.88882

From the Edited Volume

The Universe of Escherichia coli

Edited by Marjanca Starčič Erjavec

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1. Introduction

There are not so many organisms that are so well studied and researched as the bacterium Escherichia coli (E. coli). Since its discovery in 1885, it was used in research, and by end of 2018, there are now already 368,071 publications in PubMed about E. coli [1]. Figure 1, presenting data about number of publications found in PubMed for the search term “Escherichia coli” in the time frame from 1932 to 2018, clearly demonstrates the high and still growing research interest in this microbe.

Figure 1.

Number of publications in PubMed for the search term “Escherichia coli” in the time frame from January 01, 1932 to December 31, 2018 [1].


2. The discovery of Escherichia coli

The bacterium E. coli was discovered by the German-Austrian pediatrician Dr. Theodor Escherich (1857–1911) in 1885 [2]. He conducted examinations of neonate’s meconium and feces of breast-fed infants with the aim to gain insight into the development of intestinal “flora.” In preparations of meconium and stool samples under the microscope, he observed “slender short rods” of the size of 1–5 μm in length and 0.3–0.4 μm in width, which he named Bacterium coli commune (Figure 2). Further, he cultured these bacteria on agar and blood serum plates, where these bacteria grew as white, non-liquefying colonies. He also showed that these bacteria slowly cause milk to be clotted, as a result of acid formation, and demonstrated that these bacteria have fermentative ability. He also performed the Gram method of staining and revealed that these bacteria rapidly take color with all aniline dyes but lose the color after treatment with potassium iodide and alcohol [2]. Later, in 1919, the bacterium was renamed after its discoverer by Castellani and Chalmers and became Escherichia coli [3].

Figure 2.

Escherich’s drawing of the stool bacteria, as seen under light microscope [4]. Panel 1: Preparation of a meconium of a 27-hour-old infant. The E. coli as Bacterium coli commune is represented under d. Panel 2: Preparation of a stool of a 2-month-old healthy breast-fed child. The E. coli as Bacterium coli commune is represented under a and a′.


3. Characteristics of Escherichia coli

3.1 Basic characteristics

The bacterium E. coli (Figure 3) belongs into the family of Enterobacteriaceae. It is a Gram-negative rod-shaped bacterium, non-sporulating, nonmotile or motile by peritrichous flagella, chemoorganotrophic, facultative anaerobic, producing acid from glucose, catalase positive, oxidase negative, and mesophilic [5].

Figure 3.

Scanning electron microscopy of a single bacterial E. coli cell adhering to 19-day-old Caco-2 cells [6].

E. coli is a well-known commensal bacterium that is among the first colonizing bacteria of the gut after birth. It is a highly successful competitor in the human gut and is comprising the most abundant facultative anaerobe of the human intestinal microbiota [7]. As it is a facultative anaerobe, it survives when released to the environment and can be spread to new hosts. E. coli is thus an important component of the biosphere [8].

Even though E. coli is a well-known commensal bacterium, many pathogenic strains of E. coli do exist. Several highly adapted E. coli clones have acquired specific virulence factors, which confer an increased ability to adapt to new niches and allow them to cause a broad spectrum of disease, and intestinal and also extraintestinal infections [7].

3.2 The E. coli genome

The first complete E. coli genome sequence was the sequence of the K-12 MG1655 strain of E. coli, published in 1997. The sequenced strain has been maintained as a laboratory strain with minimal genetic manipulation, having only been cured of the temperate bacteriophage lambda and F plasmid. The published genome has 4,639,221 base pairs. Protein-coding genes account for 87.8% of the genome, 0.8% encodes stable RNAs, and 0.7% consists of noncoding repeats. Eleven percent of the genome are involved in regulation of gene expression and also other functions [9]. A circular map of the E. coli genome is represented in Figure 4.

Figure 4.

Circular map of the E. coli K-12 MG1655 strain.

The map is based on the K-12 MG1655 sequence data as deposited in GenBank (Accession number NC_000913) [10]. The multiplier for the ticks is 1e-6 (1.0 represents 1,000,000). In blue, the forward genes are shown, in purple the reverse genes, tRNA genes in orange, and rRNA genes in red. The map was drawn with the online tool ClicO FS, available at the Internet site [11, 12].

Genomes of pathogenic E. coli strains are general bigger, as the pathogenic strains need several special properties, so-called virulence factors. These are encoded in the virulence-associated genes (VAGs), which are frequently clustered in DNA regions called pathogenicity islands (PAIs) [13]. Often the pathogenic strains possess also extrachromosomal DNA elements, i.e., plasmids, that can also carry additional VAGs [7]. Some examples of genomes of pathogenic strains in comparison with the K-12 MG1655 strain are given in Table 1.

E. coli strain Associated with infection Chromosome size (Mbp) Number of genes in the chromosome Plasmids Plasmid size (bp) Number of genes on the plasmid
K-12 MG1655 / 4.64 4.566 / / /
O157:H7 Sakai Hemorrhagic diarrhea 5.5 5.329 pO157 92.721 85
pOSAK1 3306 3
O7:K1 IAI39 Urinary tract infection 5.13 5.092 / / /
O83:H1 NRG 857C Crohn’s disease 4.75 4.532 pO83_CORR 147.060 154
O104:H4 2011C-3493 ASM29945v1 Hemolytic-uremic syndrome 5.27 5.081 pG-EA11 1549 1
pAA-EA11 74.217 82
pESBL-EA11 88.544 94
UMN026 Urinary tract infection 5.2 5.096 p1ESCUM 122.301 156
p2ESCUM 33.809 49

Table 1.

Genomes of different E. coli strains.

Data in the table are based on data available in the genome database of the National Center for Biotechnology Information (Internet site: [14].

The most famous E. coli plasmid is the plasmid F (Figure 5). It is the paradigm plasmid for plasmid-specified transfer systems, as bacterial conjugation was first identified as a function of the F plasmid. Further, this plasmid was used to develop many of the genetic techniques commonly used to dissect prokaryotic systems, and F product analysis has been central in elucidating the basic mechanisms of plasmid replication and transmission [15].

Figure 5.

Map of the E. coli F plasmid. The map was drawn based on the complete nucleotide sequence of the F plasmid as deposited in GenBank [18].

F plasmid has two functional replication regions, RepFIA and RepFIB. The RepFIA region is believed to be primarily responsible for the typical replication properties of F [16]. The secondary replication region, RepFIB, is independently functional and can perform replication in the absence of RepFIA. F plasmid has also remnants of a third replication region, RepFIC, whose function was abolished by transposition of Tn1000 into this replication region [17]. Apart from Tn1000 also insertion sequences IS2 and IS3 are carried on F plasmid [16]. The plasmid-specified transfer system is encoded in the tra region, starting with the origin of transfer (oriT) [15].

3.3 The phylogenetic groups of E. coli

The E. coli species has an extensive genetic substructure and the methods to assess the phylogenetic relationship among E. coli strains evolved during the time. In the pre-molecular era, the E. coli diversity was studied by serotyping. Serotyping studies showed that the somatic (O) antigen, the flagellar (H) antigen, and to a lesser extent the capsular (K) antigen are useful in distinguishing E. coli strains [19]. The E. coli serotyping is complex—173 O antigens, 80 K antigens, and 56 H antigens are known—and the O, K, and H antigens can be found in nature in many of the possible combinations. The final number of E. coli serotypes is therefore very high, 50,000–100,000 or more [20].

The molecular studies of E. coli diversity began with the measurement of variations in electrophoretic mobility of enzymes derived from different E. coli strains [21]. In 1980s the multi-locus enzyme electrophoresis (MLEE) became the common technique for the study of bacterial diversity. It was found that E. coli populations evolve in a clonal manner, with recombination playing a limited role, and it also became clear that genetically distant strains can have the same serotype and that closely related strains may have different serotypes [19]. Based on the MLEE studies of 38 enzyme loci, four major phylogenetic groups among E. coli were found: A, B1, B2, and D [22]. Clermont et al. [23] established a method of rapid and simple determination of the E. coli phylogenetic groups by a triplex PCR. This genotyping method is based on the amplification of a 279 bp fragment of the chuA gene; a 211 bp fragment of the yjaA gene; and a 152 bp fragment of TSPE4.C2, a noncoding region of the genome. The presence or absence of combinations of these three amplicons is used to assign the E. coli to the phylogenetic groups: A, B1, B2, or D (Figure 6).

Figure 6.

Dichotomous decision tree to determine the phylogenetic group by the Clermont triplex PCR method [23].

However, subsequently, on the basis of multi-locus sequence typing and complete genome data, additional E. coli phylogenetic groups were recognized [24, 25]. The number of defined phylogenetic groups thus rose to eight (A, B1, B2, C, D, E, F that belongs to E. coli sensu stricto, and the eighth—the Escherichia cryptic clade I). Clermont et al. [26] thus revised their method to encompass the newly described phylogenetic groups. To enable identification of the F phylogenetic group, the new extended PCR phylotyping method employs an additional gene target, arpA, which serves also as an internal control for DNA quality. Thus, the revised PCR method is based on a quadruplex PCR, and if required, additional single PCR reactions are employed to distinguish between E and clade I, A or C, and D or E phylo-group [26] (Figure 7).

Figure 7.

Dichotomous decision tree to determine the phylogenetic group by the Clermont quadruplex PCR method [26].

Two collections of human fecal isolates were screened using the quadruplex phylo-group assignment method demonstrating that 12.8% of E. coli isolates belonged to the newly described phylo-groups C, E, F, and clade I and that strains assigned to phylo-groups A and D by the triplex method are worth to be retested by the quadruplex method, as it is likely that they are going to be reclassified [26]. Logue et al. [27] performed a comparative analysis of phylogenetic assignment of human and avian extraintestinal pathogenic (ExPEC) and fecal commensal E. coli (FEC) strains and showed that a total 13.05% of studied human E. coli strains and 40.49% of avian E. coli strains had to be reclassified. Another study using human E. coli strains isolated from skin and soft-tissue infections and fecal E. coli strains from healthy humans and also avian and brown bear fecal strains revealed that 27.60% of human, 23.33% of avian, and 70.93% of brown bear strains had to be reclassified. Moreover, a high number (12.22%) of reclassifications from the previous phylo-groups to the non-typeable (NT) group were observed among the avian fecal strains of this study. Further, a survey performed on other published data by Starčič Erjavec et al. [28] showed that also a number of other studies report occurrence of NT strains by the quadruplex method, for example, a study including 140 uropathogenic E. coli strains from Iran reported 27.14% of NT strains [29]. These data emphasizes that there is a need to search for more E. coli strains from novel environments (new hosts in not yet explored geographic regions) and to revise the PCR phylotyping method again in order to type these NT strains.

3.4 The commensal E. coli

As E. coli is a facultative anaerobe, and among the first gut colonizers, these bacteria help to establish the anaerobic environment of the gut that enables the further colonization of the gut by anaerobic bacteria [30]. After the E. coli colonization, usually the host and E. coli coexist in mutual benefit for decades [7]. E. coli gets “food and shelter,” and the host benefits due to the E. coli vitamin K production and the so-called colonization resistance. Colonization resistance is the phenomenon of protection against colonization by pathogenic bacteria, including pathogenic E. coli [31]. The niche of the commensal E. coli is the mucous layer of the colon [7]. On average five different commensal E. coli strains colonize a human host at any given time [32]. As host and the E. coli profits from their association, these E. coli could be also designated as mutualistic E. coli.

3.5 The pathogenic E. coli

E. coli is also a medically important species, as it is involved in many different types of infections. Two major groups of pathogenic E. coli exists: the intestinal pathogenic E. coli (IPEC), associated with infections of the gastrointestinal tract, and the extraintestinal pathogenic E. coli (ExPEC), associated with infections of extraintestinal anatomic sites [7]. The medical diversity of this species is nicely exhibited by its classification of pathogenic E. coli (Figure 8), the so-called E. coli pathotypes.

Figure 8.

Classification of pathogenic E. coli, based on Roy et al. [33]. The IPEC are also designated as diarrheagenic E. coli (DEC)—Although not all of the subtypes in this group necessarily cause diarrhea. STEC that cause hemorrhagic colitis and/or the hemolytic uremic syndrome are called EHEC—For enterohemorrhagic E. coli. Among ExPEC also strains associated with pneumonia, skin and soft-tissues, and infections of many other extraintestinal anatomic sites are present, though they are not yet established as separate pathotypes.

The versatility of pathogenic E. coli strains depends on their genetic makeup, on the presence of so-called virulence genes, and possession of such genes distinguishes pathogenic from nonpathogenic bacteria [34]. Virulence factors help bacteria to (1) invade the host, (2) cause disease, and (3) evade host defenses [35].

3.5.1 Adhesins and invasins

Once a bacterium reaches the host surface, in order to colonize, it must adhere to host cells. For this purpose bacteria have different fimbrial and afimbrial adhesins. Fimbrial adhesins are rod-shaped protein structures, which consists primarily of an ordered array of single protein subunits, which build a long cylindrical structure. At the top, there are proteins, adhesins, which mediate the adherence to the host’s molecules. A fimbrial adhesin is thus a structure that extends outward from the bacterial surface and establishes the contact between the bacterial surface and the surface of the host cells. Afimbrial adhesins are surface proteins important for tighter binding of bacteria to host cells. Some bacteria have evolved mechanisms for entering nonphagocytic host cells. Bacterial surface proteins that provoke actin rearrangements and thereby incite the phagocytic ingestion of the bacterium by host cells are called invasins [36]. The most known E. coli adhesins and invasins are presented in Table 2.

Adhesin/invasin Most commonly tested virulence (associated) genes
Type 1 fimbriae (Fim) fimH
P fimbriae (Pap/Prf) papC, papG
S/F1C fimbriae (Sfa/Foc) sfa/focDE
N-Acetyl-d-glucosamine-specific fimbriae (Gaf) gafD
M-Agglutinin (Bma) bmaE
Bifunctional enterobactin receptor/adhesin (Iha) iha
Afimbrial adhesin (Afa) afa/draBC
Invasion of brain endothelium (IbeA) ibeA
Colonization factor antigen I (CFA/I) cfaB
Bundle-forming pili (BFP) bfpA
Intimin eaeA
Aggregative adherence fimbriae (AAF/I) aaf/I

Table 2.

Typical adhesins and invasins of pathogenic E. coli strains.

3.5.2 Iron acquisition mechanisms

Iron is essential for bacterial growth, but iron concentrations in nature are generally quite low, particularly low in host organism. To survive in the host organism, bacteria must have some mechanisms for acquiring iron. The best studied type of bacterial iron acquisition is the siderophores. These are low-molecular-weight compounds that chelate iron with very high affinity [36]. The most known E. coli iron uptake systems are presented in Table 3.

Iron uptake system Most commonly tested virulence (associated) genes
Aerobactin (Iuc) iucD, iutA
Yersiniabactin (Ybt) fyuA, irp2
Salmochelin (Iro) iroCD, iroN
Siderophore receptor IreA ireA
Temperature sensitive hemagglutinin (Tsh)—in birds, Hemoglobin protease (Hbp)—in humans tsh, hbp
Periplasmic iron binding protein (SitA) sitA
Ferrichrome-iron receptor (Fhu) fhuA

Table 3.

Typical iron uptake systems of pathogenic E. coli strains.

3.5.3 Systems to evade host immune response

The healthy host usually has multilayered defenses that prevent the establishment of bacterial infection. Among the most effective of these defenses is the immune response. However, bacteria have evolved systems to avoid, subvert, or circumvent innate host defenses and to evade acquired specific immune responses of the host [34]. A capsule is a loose, relatively unstructured network of polymers that covers the surface of a bacterium. The role of capsules in bacterial virulence is to protect bacteria from the host’s inflammatory response [36]. Further, increased serum resistance is often found among pathogenic bacteria, especially those associated with systemic infections [36]. Serum resistance is the ability to prevent complement activation on the bacterial cell surface and to inhibit insertion of the membrane attack complex into the bacterial membrane [34]. The feature is often based on the modifications in lipopolysaccharide (LPS), which can be of two types: either attachment of sialic acid to LPS O antigen or changes in the LPS O antigen side chain [36]. However, other proteins can also be implicated in increased serum resistance; for example, the TraT protein of the surface exclusion complex involved in conjugation [37]. Another important protein of pathogenic E. coli is the Toll/interleukin-1 receptor domain-containing protein (Tcp) that interferes with the TLR signaling system of the innate immunity [38]. The most known E. coli systems to evade host immune response are presented in Table 4.

Host immunity evading system Most commonly tested virulence (associated) genes
Group II capsule including K1 and K5 capsules kpsMT II
Conjugal transfer surface exclusion protein (TraT) traT
Outer membrane protease T (OmpT) ompT, APEC-ompT
Increased serum survival (Iss) iss
Suppression of innate immunity (Toll/interleukin-1 receptor domain-containing protein Tcp) tcpC

Table 4.

Typical host immunity evading systems of pathogenic E. coli strains.

3.5.4 Toxins

Toxins are the virulence factors that damage the host. Exotoxins are toxic bacterial proteins that are excreted into the medium by growing bacteria or localized in the bacterial cytoplasm or periplasm and released during bacterial lysis. Exotoxins vary considerably in their activities and the target host cell types [36]. The most known E. coli toxins (exotoxins) are presented in Table 5.

Toxins Most commonly tested virulence (associated) genes
alpha-Hemolysin (HlyA) hlyA
Cytotoxic necrotizing factor 1 (CNF-1) cnf1
Cytolethal distending toxin IV (CDT 1) cdtB
Uropathogenic specific protein (Usp) usp
Colibactin (Clb) clbAQ
Serine protease autotransporters Sat, Pic sat, picU
Heat-stable toxins (STa, STb) stIa/stIb
Heat-labile toxin I (LTI), heat-labile toxin II (LTII) eltI, eltIIa
Shiga toxin 1 (Stx1), Shiga toxin 2 (Stx2) stxI, stxII
EHEC hemolysin (Ehx) ehxA
Low-MW heat-stable toxin (EAST1) astA

Table 5.

Typical toxins (exotoxins) of pathogenic E. coli strains.

However, E. coli possess also an endotoxin, namely, the lipopolysaccharide, which is an integral component of the outer membrane of Gram-negative bacteria. The lipid portion (lipid A) is embedded in the outer membrane, with the core and O antigen portions extending outward from the bacterial surface. Lipid A is the toxic portion of the molecule, and it exerts its effects only when bacteria are lysed. The toxicity of lipid A resides primarily in its ability to activate, complement, and stimulate the release of bioactive host proteins, such as cytokines [36].

3.6 The antibiotic-resistant E. coli

Antibiotics are low-molecular-weight compounds that kill or inhibit growth of bacteria [36]. Antibiotic treatment is one of the main approaches of modern medicine to combat bacterial infections, including also E. coli infections [39]. However, bacteria evolved different mechanisms that confer resistances to antibiotics. Resistant bacteria are able to either (i) modify/degrade the antibiotic, (ii) actively transport the antibiotic out of the cell or prevent its intake, (iii) sequester the antibiotic by special proteins, or (iv) modify, bypass, or protect the target [40]. The emergence, spread, and persistence of resistant and even multidrug-resistant (MDR) bacteria or “superbugs”, also among E. coli, are now posing a serious global health threat of growing concern [39]. The antimicrobial resistance surveillance data of European Centre for Disease Prevention and Control (ECDC) also showed the increase in antibiotic resistance among invasive E. coli isolates (Figure 9).

Figure 9.

Prevalence of invasive E. coli isolates with antimicrobial resistance to aminopenicillins, fluoroquinolones, third-generation cephalosporins, aminoglycosides, and carbapenems—the population weighted mean EU/EEA is shown. The prevalence of antimicrobial resistance to carbapenems in 2009 and 2011 was 0%, in 2012 <0.1%, in 2013 and 2015 0.2%, and in 2014, 2016, and 2017 0.1% [41, 42, 43, 44, 45, 46, 47, 48, 49].

The mechanisms of resistance to antibiotics are encoded in resistance genes. A list of typical E. coli resistance genes is given in Table 6.

Resistance gene(s) Antibiotic class Resistance to
strA [aph(3′)-Ib], strB [aph(6′)-Id] Aminoglycosides STR
aadA1, aadA2, aadA5, aadA7, aadA24 Aminoglycosides STR
aph(3′)-Ia Aminoglycosides KAN
aac(3′)-VI, aac(3′)-IId Aminoglycosides GEN
blaTEM-1 β-Lactams AMP
blaOXA-1 β-Lactams AMP
blaCMY-2 β-Lactams AMC, AMP, CRO, FOX, TIO
ampC β-Lactams AMC, AMP, FOX
sul1, sul2, sul3 Folate synthesis inhibitors FIS
dfrA1, dfrA5, dfrA12, dfrA17 Folate synthesis inhibitors SXT
mphA Macrolides AZM
floR Phenicols CHL
cmlA Phenicols CHL
catA1, catB3 Phenicols CHL
qnrB2, qnrB6, qnrS2 Quinolones NAL, CIP
tet(A), tet(B), tet(C), tet(D), tet(M) Tetracyclines TET

Table 6.

Typical E. coli resistance genes.

STR, streptomycin; KAN, kanamycin; GEN, gentamicin; AMP, ampicillin; AMC, amoxicillin/clavulanic acid; CRO, ceftriaxone; FOX, cefoxitin; TIO, ceftiofur; FIS, sulfisoxazole; SXT, trimethoprim/sulfamethoxazole; AZM, azithromycin; CHL, chloramphenicol; NAL, nalidixic acid; CIP, ciprofloxacin; TET, tetracycline [50].

As many of the resistance genes are encoded on conjugative plasmids or conjugative transposons, they are easily transferred between different bacteria and hence spread in the population [36].

3.7 The bacteriocinogenic E. coli

Bacteriocins are ribosomally synthesized, proteinaceous substances that inhibit the growth of closely related species through numerous mechanisms [51]. They are a heterogeneous group of particles with different morphological and biochemical entities. They range from a simple protein to a high molecular weight complex [52]. The bacteriocins with molecular masses below 10 kDa are designated as microcins [53]. Bacteriocins are potent toxins that are usually produced during stressful conditions and result in the rapid elimination of neighboring bacterial cells that are not immune or resistant to their effect. The killing is exhibited after adsorption to specific receptors located on the external surface of sensitive bacteria, by one of the three primary mechanisms: forming channels in the cytoplasmic membrane, degrading cellular DNA/RNA, or inhibiting protein synthesis. Because of their narrow range of activity, it has been proposed that the primary role of bacteriocins is to mediate intraspecific, or population level, interactions [54]. The genetic determinants of most of the bacteriocins are located on the plasmids, apart from few, which are chromosomally encoded [52]. Bacteriocins of E. coli are usually called colicins. A relatively high frequency of colicin-encoding plasmids is found in isolates of pathogenic E. coli [55], for example, ~80% of O157:H7 enterohemorrhagic E. coli strains studied by Bradley and Howard were colicinogenic [56]. Especially microcins have been associated with pathogenic strains [54]. In a collection of E. coli strains isolated from skin and soft-tissue infections, 55% of strains possessed microcin M, and 43% possessed microcin H47 [57]. Further, colicin insensitivity among these strains correlated with a higher prevalence of extraintestinal virulence factors [58]. Typical E. coli bacteriocins, their receptors, translocation systems, and mode of action are given in Table 7.

Bacteriocin Receptor Translocation system Mode of action
ColA BtuB Tol Ion channel
ColB FepA Ton Ion channel
ColD FepA Ton Stops translation
ColE1 BtuB Tol Ion channel
ColE2 BtuB Tol DNA-endonuclease
ColE3 BtuB Tol rRNA-endonuclease
ColE4 BtuB Tol rRNA-endonuclease
ColE5 BtuB Tol Stops translation
ColE6 BtuB Tol rRNA-endonuclease
ColE7 BtuB Tol DNA-endonuclease
ColE8-J BtuB Tol DNA-endonuclease
ColIa Cir Ton Ion channel
ColIb Cir Ton Ion channel
ColK Tsx Tol Ion channel
ColM FhuA Ton Inhibition of peptidoglycan synthesis
ColN OmpF Tol Ion channel
ColS4 OmpW Tol Ion channel

Table 7.

Typical E. coli bacteriocins, their receptor, translocation system, and mode of action [59, 60].

3.8 The probiotic E. coli

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Probiotic bacteria act via a variety of means, including modulation of immune function, production of organic acids and antimicrobial compounds, interaction with resident microbiota, interfacing with the host, improving the gut barrier integrity, and enzyme formation [61]. Several E. coli strains were recognized as good and effective probiotics and are now used in drugs (see Table 8). The probiotic E. coli are applied to a variety of human conditions, including intestinal bowel diseases and diarrhea. Further it was shown that colonization of newborns led to reduced disease rates, lower incidence of allergies, and reduced mortality [62].

Drug name Mutaflor Symbioflor 2 Colinfant newborn
E. coli strain E. coli Nissle 1917 strain Six different E. coli strains (G1/2, G3/10, G4/9, G5, G6/7, and G8) E. coli A0 34/86 strain
Product Capsules Suspension Powder for preparation of per oral solution
Produced by Ardeypharm GmbH, Herdecke, Germany SymbioPharm GmbH, Herborn, Germany Dyntec, Terezín, Czech Republic
Contents 2.5–25 × 109 CFU/capsule 1.5–4.5 × 107 CFU/ml 0.8–1.6 × 108 CFU/dosis
Recommended daily dose 1–2 capsules/day (2.5–50 × 109 CFU) 2–4 ml (3.0–18 × 107 CFU) 0.8–1.6 × 108 CFU three times/week
Isolation date of the used strain(s) 1915 1954 Data not available
Serotype 06:K5:H1 Variable including 035,129, 0:169, rough, all H– 083:K24:H31
Plasmid content 2 cryptic plasmids 12 plasmids No plasmids
Microcin production Microcin M, H47 Microcin S Data not available
Motility Motile (flagella present) Nonmotile (flagella absent) Data not available
Closest relatives CFT073, ABU83972 (UPEC) K12, ATCC8739 (commensals) CFT073, 536 (UPEC)
Year of first publication describing the use in humans 1989 1998 1967

Table 8.

Probiotic E. coli drugs [62, 63].

E. coli Nissle 1917 is nowadays often used as a reference strain or model microorganism in experimental biomedical studies, including recombinant manipulations of the strain in order to construct derivatives with novel properties [64]. One such example is the strain ŽP, which is a genetically modified Nissle 1917 possessing a bacterial conjugation-based “kill”-“anti-kill” antimicrobial system—a conjugative plasmid carrying the “kill” gene (colicin ColE7 activity gene) and a chromosomally encoded “anti-kill” gene (ColE7 immunity gene). Hence, in the process of conjugation, the conjugative plasmid transfers the “kill” gene into a recipient cell, where it is expressed and the recipient killed [65, 66].

3.9 The “workhorse” E. coli

E. coli is known for its fast growing rate in chemically defined media and extensive molecular tools available for different purposes. All these make it an important model organism, which is also called the “workhorse” of molecular biology. Even though E. coli lacks many interesting features appreciated in biotechnology, such as growing at extreme temperatures or pH and the capacity to degrade toxic compounds, pollutants, or difficult to degrade polymers, it is much used in biotechnology also [67]. In Table 9 contributions of E. coli to biology, medicine, and industry are listed.

Contribution Authors Year
Molecular biology, physiology, and genetics
Elucidation of the genetic code Crick FH, Barnett L, Brenner S, and Watts-Tobin RJ 1961
DNA replication Lehman IR, Bessman MJ, Simms ES, and Kornberg A 1958
Transcription Stevens A 1960
Life cycle of lytic bacteriophages Ellis EL and Delbrück M 1939
Gene regulation of the lac operon Jacob F and Monod J 1961
Gene regulation of the ara operon Englesberg E, Irr J, Power J, and Lee N 1965
Discovery of restriction enzymes Linn S and Arber W 1968
Identification of genes controlling antimicrobial drug tolerance in stationary phase Hu Y and Coates AR 2005
Role of global regulators and nucleotide metabolism in antibiotic tolerance Hansen S, Lewis K, and Vulić M 2008
Metabolic control of persister formation Amato SM, Orman MA, and Brynildsen MP 2013
Swarming motility behavior Harshey RM and Matsuyama T. 1994
Elucidation of the structure and function of ATP synthase Capaldi RA, Schulenberg B, Murray J, and Aggeler R 2000
Conjugal DNA transfer Tatum EL and Lederberg J 1947
Random nature of mutation Luria SE and Delbrück M 1943
Relationship between genomic evolution and adaptation Barrick JE, Yu DS, Yoon SH, Oh TK, Schneider D, Lenski RE, and Kim JF 2009
Role of adaption, chance, and history in evolution Travisano M, Mongold JA, Bennet AF, and Lenski RE 1995
Adaptive mutation Cairns J, Overbaugh J, and Miller S 1988
Role of historical contingency in evolution Blount ZD, Borland CZ, and Lenski RE 2008
Origin of novel traits Blount ZD, Barrick JE, Davidson CJ, and Lenski RE 2012
Long-term fitness trajectories Wiser MJ, Ribeck N, and Lenski RE 2013
Effect of sexual recombination on adaptation Cooper TF 2007
Predator-prey interactions (bacteriophage) Chao L and Levin BR 1977
Genetic engineering and biotechnology
Molecular cloning and recombinant DNA Cohen S, Chang A, Boyer H, and Helling R 1973
Generating precise deletions and insertions Link AJ, Phillips D, and Church GM 1997
Gene replacement Herring CD, Glasner JD, and Blattner FR 2003

Table 9.

Contributions of E. coli to biology, medicine, and industry [68, 69, 70].

The following recombinant pharmaceuticals were set up to be in vivo synthesized in E. coli: insulin, interleukin-2, human interferon-β, erythropoietin, human growth hormone, human blood clotting factors, pegloticase, taxol, and certolizumab. Further, E. coli is also used to produce biofuels and industrial chemicals such as phenol, ethanol, mannitol, and a variety of others [68].


4. Conclusion

To conclude, E. coli is a truly versatile microorganism possessing many facets—it is a well-known commensal bacterium, but some strains can be also pathogenic, even causing mortality, especially if the pathogenic strain acquired multiple resistance genes. However used as a probiotic it can improve health and in it can be employed as a good working “workhorse” in the laboratory as well as in biotechnological settings. The differentiation between commensal and pathogenic strains is not easy, as among the healthy gut microbiota pathogenic strains are hidden, and also commensal strains can become pathogenic due to horizontal gene transfer of mobile genetic elements possessing virulence genes [71]. Even though E. coli has been the object of research now for already more than 100 years, its versatility warrants new possibilities for investigation also in the future.



The author is thankful to the Slovenian Research Agency (P1-0198) for its funding.


Conflict of interest

The author has no conflict of interest.


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Written By

Marjanca Starčič Erjavec

Published: 18 September 2019