The categorization of
Urinary tract infections (UTIs) rank second among infectious diseases around the world, and this makes them significant. There are many microbial agents which may cause UTIs. Enterobacteriaceae family members are recognized as important UTI bacterial causative agents. Among them, uropathogenic Escherichia coli (UPEC) pathotypes are considered as the most important bacterial agents of UTIs. Today, genomics and bioinformatics explain us why UPEC strains are so considerable pathogens regarding UTIs. There is a diversity of E. coli strains involving commensal and pathogenic strains. Genomics shows that commensal strains of E. coli encompass the minimal amount of genome and genetic elements among E. coli populations, whereas the pathotypes of E. coli possess the maximal or a big portion of genomic elements. Previous studies confirm the presence of a vast range of virulence genes within the pool of E. coli pathotypes like UPEC. So, the pool of virulence genes (virulome) belonging to UPEC enables UPEC pathotypes to have huge genomes with the ability of different levels of pathogenesis. The more virulence factors, the more pathogenicity. Due to the presence of a mass of virulence factors within UPEC cellular structures, well-known fimbrial adhesins in UPEC pathotypes are discussed in this chapter.
- uropathogenic Escherichia coli
- virulence factors
- urinary tract infections
UTIs with second ranking are one of the most dominant infectious diseases around the world. Although UTIs include vast etiological microbial agents, two pathogenic microorganisms such as
The pangenomic and phylogenetic studies have revealed five different categories within the species of
1.1. Biology of urinary tract infections
There are different types of UTIs with a diversity of clinical demonstrations. Today, we know that the UTI syndromes are completely in association with hosts’ immune system activities, type of causative microbial agent and the contributed microbial virulence factors. UTIs may be appeared as acute or chronic lower (typically known as cystitis) and/or upper (typically known as pyelonephritis) urinary tract infections, with symptomatic or asymptomatic manifestations and complicated or uncomplicated demonstrations. So, asymptomatic bacteriuria and simple cystitis with some ignorable irritations may be recognized as light and mild UTIs, respectively; while the urosepsis is known as a serious deathful type of UTI. Generally, the uncomplicated UTIs are recognized in patients with no previous background for UTIs, whereas the complicated UTIs normally happen in patients with previous problems in their urinary tracts. The remarkable point of view is the association between predisposing factors of diabetes, sexual intercourse, gender, catheterization, pregnancy, overweight, genetic factors, host’s immune system responses and the type of UTIs and their severities [3, 5, 8, 9, 10, 11, 12].
In accordance with previous surveys, there are several numbers of microbial pathogens which can be identified as UTI pathogenic microorganisms. The microbial pathogens depending on the type of UTIs involve a vast number of pathogenic causative agents including Gram-negative bacteria, e.g. UPEC,
1.2. The genus of
Escherichia: A great bacterial empire
The genus of
Escherichia coliand pangenomics
The term pangenome was applied by Sigaux for a database with the content of tissues and tumour genomic data; but the application of pangenome with its microbial content was used by Tettelin and colleagues for the first time, and this refers to a collection of genes and genetic elements in a family group which can be recognized among species of a genus. According to genomic studies, each microbial genus encompasses a main genomic pool which is known as core genome. The core genome contains all those vital genes belonging to different species of a microbial genus. In addition to core genome, there is a group of genomic materials pertaining to species members of a genus which is named as extra genome (flexible or accessory genome). Sometimes some accessory genome pools contain unique genes which are completely related to specific strain. The extra genome possesses genes that are vital but varies in different genome pools. Some genera bear closed pangenomes, whereas the others contain open pangenomes. The open pangenomic microbial organisms involve a vast range of strains. In parallel with molecular techniques, bioinformatics has a key role in pangenomics. Computational analyses give us brilliant information regarding chromosomal genes and motile genetic elements such as plasmids, transposons and phages. Today, the bacterial genus of
The complete genomic data regarding
The reported results from previous studies show that the commensal strains of
Table 2 shows a number of well-known databases in which the genomic data regarding
|Database||The main subject||URL||Reference|
|Kyoto Encyclopedia of Genes and Genomes|
|Genes, genomes, etc.||http://www.genome.jp/kegg/|
|SHared Information of GENetic Resources (SHIGEN)||The profiling of |
|Pfam 31.0||Protein family database||http://pfam.xfam.org/|||
(The European Bioinformatics Institute (EMBL-EBI))
|The DNA Data Bank of Japan (DDBJ)||Nucleotide sequence database||http://www.ddbj.nig.ac.jp/|||
(National Center for Biotechnology Information (NCBI))
|Nucleotide sequence database||http://www.ncbi.nlm.nih.gov/genbank/|||
The pangenomic studies reveal an interesting evolutionary relationship between
The UTIs are divided into community-acquired and nosocomial infectious diseases. The UPEC pathotypes are the most dominant causative bacterial agents of UTIs. As previous investigations show, about 50% of nosocomial and up to 95% of community-acquired UTIs are occurred by UPEC strains. So, the UPEC pathotypes are one of the most considered UTI causative agents worldwide. These reports lead us to a wide variety of virulence factors in UPEC pathotypes. Besides, the bioinformatic approaches and pangenomics confirm the presence of a giant treasure of virulence genes within the pangenome of UPEC [7, 8, 35, 47].
The spread of virulence genes among UPEC pathotypes is quite different. The range of UTIs varies from ignorable cases like asymptomatic bacteriuria to deathful cases like urosepsis. The severity of UTIs is completely in association with the UPEC virulence gene pool (virulome). Sometimes, pathotypes undergo mutations in their hosts’ bodies which may lead to lose their own virulence genes. It seems that the UPEC pathotypes, which may cause asymptomatic bacteriuria, have undergone virulence gene deletions. On the other hand, strong uropathogenic strains encompass a mass of virulence genes which enable them to occur severe UTIs within their hosts’ bodies. The occurrence of UTIs is associated with the host’s genetic predisposing factors, immune system, gender, hospitalization, catheterization, social behaviour, sexual activities, personal hygiene and the presence of virulence factors in uropathogenic microbial agents [3, 7, 11, 13, 22, 48, 49, 50].
The outcomes of several studies reveal the presence of a huge number of virulence factors which have been expanded among different strains of UPEC. Here, the most considerable virulence factors are mentioned and the most considerable filamentous adhesins are explained one by one.
Escherichia coli(UPEC) virulome
The severity of UPEC pathogenesis is completely in association with diversity of virulence genes in their pangenomes. Figure 3 shows the pangenome of UTI89. The virulence genes may be located on chromosomes (added through vertical gene transfer) or plasmids, transposons, integrons and phages (added via horizontal gene transfers). Previous studies indicate that the majority of virulence genes belonging to UPEC are located on pathogenicity islands (PAIs) where many of genes are transferred from other species rather than
Because of the vast variety of pathogenicity potentials in UPEC strains, only hair-like structures of afimbrial adhesins (including curli and Afa) and fimbrial adhesins (comprising Dr, Type 1 fimbriae, Type 3 fimbriae, F1C fimbriae, S fimbriae, P fimbriae, Auf and F9 fimbriae) are discussed in this chapter. There are some useful databases such as Center for Genomic Epidemiology (https://cge.cbs.dtu.dk/services/VirulenceFinder/) and Virulence Factors of Pathogenic Bacteria (http://www.mgc.ac.cn/VFs/) which may be used for detection and identification virulence genes within the
4.1. Filamentous adhesin virulome
Each microorganism either pathogen or non-pathogen needs to be adhered for colonization. Indeed, colonization of pathogenic microorganisms results in pathogenesis within human body’s host. For this reason, UPEC has a range of superficial proteins and adhesins (Table 3). However the hair-like structured fimbriae are invaluable virulence factors which enable UPEC pathotypes to have successful attachment, colonization, biofilm formation and virulence [7, 22, 53, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65].
Fimbrial adhesins are superficial peritrichous arranged exterior proteinaceous appendages which target special motifs upon the cell surface receptors to join them in the manner of key-and-lock operation. These adhesins are able to attach onto biotic (e.g. host cells) and abiotic (e.g. catheter) surfaces. The aforementioned characteristics make UPEC bacteria functional and effective pathogenic microorganisms. The attachment of bacterial cells of UPEC onto the host cells is a complicated process which may be caused by important proteinaceous molecules of adhesins. Adhesins prepare suitable condition for a successful signalling controlled communication between UPEC cells and human body cells. In other words, the fimbrial adhesins act as signal molecules. As shown in Table 3, the most studied and recognized superficial filamentous adhesins are Curli, Dr, AFA, Type 1 fimbriae, Type 3 fimbriae, F1C fimbriae, S fimbriae, P fimbriae, F9 fimbriae and Auf. Some of these superficial fimbrial organelles involving F1C, P, S, Auf, Type 1, Type 3 and F9 fimbriae are categorized into chaperone-usher (CU) proteins [8, 27, 53, 59, 62, 66].
4.1.1. Curli adhesins
Curli adhesins of UPEC are known as types of fragile exterior proteinous coiled fibrous appendages which contribute in linking the UPEC cells onto related receptors situated upon the human body cells such as endothelial cells, epithelial cells, matrix proteins, urothelial cells, mucosal cells, blood cells, etc. In addition to UPEC pathotypes, curli adhesins are recognized in
4.1.2. Dr/Afa adhesins
The Dr and Afa adhesins are the members of DR family. Dr adhesins (with a homology rate of ≥70%) and Afa molecules are able to bind to the Dra blood group antigen molecules situated onto the decay-accelerating factors (DAFs). The DAF molecules are located upon the surface of different types of cells such as urothelial cells. The Dr gene operons consisted of five genes, including
4.2. Chaperone-usher fimbrial adhesins
There are varieties of fimbriae which are produced by Gram-negative bacteria such as
4.2.1. Type 1 fimbriae
Type 1 fimbriae as mannose-sensitive adhesins (belonging to chaperone-usher class) are able to attach to those receptors with mannose residues. Uroplakin molecules with high frequency in human urine bladder are known as one of the most important Type 1 fimbriae receptors. Furthermore, there are different types of Type 1 fimbriae receptors which are located on human ureter and Henle’s tubules. These fimbriae are encoded in 99% of commensal and pathogenic strains of
4.2.2. Type 3 fimbriae
Type 3 fimbriae are encoded by
4.2.3. F1C fimbriae
The F1C fimbriae are encoded by a gene operon consisting of seven genes of
4.2.4. S fimbriae
In addition to FIC, the S fimbriae organelles have also a close morphology to F9, P and Type 1 fimbriae and are detected in ≥22% of the UPEC pathotypes. The S fimbriae are encoded by
4.2.5. P fimbriae
P fimbriae as considerable adhesins are encoded by 11 genes within a gene operon of
4.2.6. Auf fimbriae
Auf (acronym for another UPEC fimbria) fimbriae are detected in 67% of isolated UPEC pathotypes. The Auf fimbriae are encoded by the gene operon of
4.2.7. F9 fimbriae
The F9 fimbriae encoded by
5. Diagnostic methods for virulence genes of filamentous adhesins
Detection and identification of genes such as virulence genes of filamentous adhesins may be achieved by a vast range of molecular techniques. PCR tools from conventional and multiplex to real time are the commonest molecular diagnostic techniques which can be used for limited samples [80, 81, 82, 83, 84, 85, 86].
Furthermore there are advanced pangenomic techniques like microarray technology which can be applied for detection and identification of different types of genes, when there are huge numbers of specimens. Microarray technology is divided into three types of DNA, protein and RNA microarray tools. The outcome of microarray technology is reliable, sensitive, specific, flexible and rapid with high accuracy [4, 7, 8, 87, 88, 89, 90, 91, 92, 93].
UPEC strains are expanded pathogenic microorganisms which are able to carry a mass of virulence genes within their genomes. The environmental condition and the genomic abilities and capacity determine the expression of virulence genes and factors. The UPEC strains bear different types of virulence factors in different parts of their cellular structures. These properties make UPEC pathotypes interesting pathogenic microorganisms which can appear a vast range of UTIs: from acute to chronic, from light to severe, from complicated to uncomplicated, from lower to upper and from asymptomatic to symptomatic signs and syndromes. So, knowing the genotypic and phenotypic characteristics of UPEC strains in different regions of world helps us to recognize the probable UPEC strains with their local clinical demonstrations. This enables us to have an accurate diagnosis with a definite treatment to reduce the healthcare costs around the world. Moreover, equipped microbiology laboratories with normal molecular tools and techniques like PCR or advanced pangenomic technologies support us to have specific, sensitive and reliable outcome.