|Year : 2020 | Volume
| Issue : 1 | Page : 13-22
Virulence markers, phylogenetic evolution, and molecular techniques of uropathogenic Escherichia coli
Etefia U Etefia, Solomon A Ben
Department of Medical Laboratory Science, University of Calabar, Calabar, Nigeria
|Date of Submission||17-Jul-2019|
|Date of Decision||17-Aug-2019|
|Date of Acceptance||27-Aug-2019|
|Date of Web Publication||06-Jan-2020|
Etefia U Etefia
Department of Medical Laboratory Science, University of Calabar, Calabar
Source of Support: None, Conflict of Interest: None
Urinary tract infections are very significant public health concerns globally with most of them being caused by uropathogenic Escherichia coli (UPEC). The wide range of genetic makeup of UPEC due to the acquisition of specialized virulence genes located on mobile genetic elements called pathogenicity islands is the rationale behind colonization of the urinary tracts of humans as against diarrheagenic E. coli pathotype. Indebt understanding of the virulence mechanisms and pathogenesis of UPEC lies in the knowledge of the molecular techniques of UPEC which have advanced tremendously. This review has carefully summarized the unique virulence markers, the phylogenetic evolution, and molecular techniques used in the studies of pathogenesis and virulence of UPEC.
Keywords: Molecular techniques, phylogenetic evolution, uropathogenic Escherichia coli, urinary tract infection
|How to cite this article:|
Etefia EU, Ben SA. Virulence markers, phylogenetic evolution, and molecular techniques of uropathogenic Escherichia coli. J Nat Sci Med 2020;3:13-22
|How to cite this URL:|
Etefia EU, Ben SA. Virulence markers, phylogenetic evolution, and molecular techniques of uropathogenic Escherichia coli. J Nat Sci Med [serial online] 2020 [cited 2022 Nov 30];3:13-22. Available from: https://www.jnsmonline.org/text.asp?2020/3/1/13/269240
| Introduction|| |
Escherichia More Details coli are normal flora of the gastrointestinal tract of humans and animals which help in maintaining a balance between microbial community, internal physical, and chemical factors of the gastrointestinal environment. However, in the immunosuppressed individuals or a violated gastrointestinal environment, these strains E. coli which do not cause disease, could become pathogenic. Some of these nondisease causing strains of E. coli acquire specific virulence factors (via DNA horizontal transfer of transposons, plasmids, bacteriophages, and pathogenicity islands [PAIs]), which allows them to survive in their new habitats and establish a wide range of disease conditions.
The disease-causing E. coli strains are broadly classified as either diarrheagenic E. coli (DEC) or extraintestinal E. coli (ExPEC). DEC pathotypes cause gastroenteritis and rarely establish disease beyond the gastrointestinal tract while ExPEC pathotypes are capable of existing in the gastrointestinal tracts but are capable of spreading and causing diseases in other parts of the body such as diseases of the blood, the circulatory system, the central nervous system, and the urinary tract.
Of all the ExPEC, uropathogenic E. coli (UPEC), which causes urinary tract infections (UTIs) has the greatest medical importance. This is because UTIs affect every category of human with most of them being caused by UPEC., These bacteria are associated with both asymptomatic bacteriuria and symptomatic UTIs. UTIs are categorized base on the parts of the body which the infections occur. These are cystitis which occurs in the bladder, pyelonephritis which occurs in the kidney and bacteriuria, which occurs in the urine.,,,
UPEC could cause symptomatic UTIs because of a wide range of virulence factors acquired by these bacteria, particularly adhesive molecules which have been acknowledged to be the most important determinants of pathogenicity., Although the mechanisms of asymptomatic bacteriuria are not properly understood, a number of reports have attributed asymptomatic bacteriuria to the inability of UPEC to acquire the adhesive molecules or have even lost the molecules making them nonadherent and nonhemolytic.,,
Due to the variability of genetic content of UPEC and the possible genetic transfer between UPEC and DEC, it is important to understand the basis of their genetic differences, evolution of DEC to UPEC and the relevant molecular techniques used in the study of these organisms. Hence, the present study aimed to review the important virulent markers, phylogenetic evolution, and molecular techniques used in the studies of pathogenesis and virulence of UPEC.
| Genetic Markers and Their Roles in Uropathogenic Escherichia Coli virulence|| |
Strains of UPEC have virulence factors which favor their adaptation in the urinary tract and allow them to break the barriers of very strong immune systems. Furthermore, UPEC strains have a broad spectrum genetic makeup due to the ability of these strains to acquire specific virulence genes usually found on PAIs (mobile genetic elements)., Virulence factors of UPEC are classified into two categories: (i) bacterial cell surface virulence factors and (ii) bacteria secreted virulence factors.
Bacterial cell surface virulence factors
Different types of organelles such as fimbriae and pili used for adhesion by UPEC to the urinary tract of the human host produce adhesins (adhesive molecules) which play the greatest virulent roles in the pathogenicity of UPEC. The roles of these adhesins include: (i) direct triggering pathways of the host and signaling of the pathways of bacterial cell, (ii) delivery of other products of the bacteria to the host tissues, and (iii) invasion of the bacteria into the host cells.
| Adhesins and Biofilms Production|| |
Studies have reported that type I fimbriae play the most significant role in animal UTIs, but their roles in human UTIs are still not understood. This is because the fimbriae are found in both the pathogenic and the nonpathogenic strains of UPEC.,,,,,, According to Plos et al., the difference between the frequencies of fim genes (which code for type 1 fimbriae) in both UPEC and the nondisease causing strains of E. coli is not significant.
Type 1 fimbriae facilitate the survival of the bacteria, the stimulation of the inflammation of the mucosa, bacterial invasion, bacterial growth, and production of biofilm. There is also a binding between urothelial mannosylated glycoproteins uroplakin Ia and IIIa) through the adhesin subunit FimH found at the tip of the fimbria and the type 1 fimbriae which results to phosphorylation of molecules. This stimulates the signaling of pathways involved in bacterial invasion, programmed cell death (apoptosis) and may also mediate the increase in the level of intracellular Ca2+ of urothelial cells.,, However, Tamm–Horsfall Protein is secreted by the kidney cells into urine which functions as a soluble FimH receptor to obstruct interaction of host cells with the bacteria, thus, reducing the infection and survival of UPEC urogenital system.,
Although most studies have confirmed that type 1 fimbriae play a vital role in the colonization of bladder colonization by UPEC,, the prevalence of UPEC strains range from 71% among isolates from cystitis patients 58% among those from patients with asymptomatic bacteriuria, with fecal strains in the mid-range at 60%. However, in contrast, the level of expression of type 1 fimbriae among UPEC blood isolates (81%) is significantly different from that of fecal strains.,
In the pathogenesis of human ascending UTIs and pyelonephritis, cytokines are produced byPfimbriae (the second-most prominent virulence factor of UPEC) through the adherence of UPEC to the matrix of the mucosa and tissues.,,,,,Pfimbriae contain heteropolymeric fibers which are made of diverse protein subunits of papA-K gene operon which recognize kidney glycosphingolipids and carries the Gal α (1–4) Gal determinant on renal epithelia by its binding to papG.,, This binding produces ceramide which antagonizes Toll-like receptor 4 resulting in the development of UTIs associated inflammation and pain., ThePfimbriae allow for the early infections of the epithelial cells of the renal tubules by the UPEC while the type 1 fimbriae enhance the infection of the center of the tubule through interbacterial binding and biofilm formation. These cause ineffective renal filtration resulting to complete blockage of the nephron resulting to disease condition called pyelonephritis.
According to Soto, bacterial biofilms play an important role in medicine and has major health implications in urology. Uroepithelial bacteria which form biofilms are often implicated with pyelonephritis and chronic or recurrent infections. Several studies reported that most of the isolates collected from patients with recurrent infections were biofilm producers in vitro. Aside UPEC strains, the expression of biofilms has been considered a consensual virulence factor among EAEC isolates. In EAEC strains, biofilm formation is a complex event that may involve multiples adhesins and factors not devoted to adhesion.
Biofilm production by E. coli is important in determining its virulence factor by contributing to the bacterial resistance.,,,, Recent reports have shown that biofilm produced by E. coli mediated by co-expression of curli and cellulose facilitates the survival of UPEC in the urinary tract for a long time through the production of an inert, hydrophobic extracellular matrix which surrounds the organism.,, Most studies of biofilm formation in UTI have addressed its role in recurrent diseases of UPEC. Curli belongs to a class of fibers known as amyloids which helps in adhesion to surfaces, cell aggregation, and the development of biofilm by bacteria. Curli are encoded in the curling subunit gene (csg) gene cluster, made up of two differently transcribed operons. The csgB, csgA, and csgC genes are coded by one operon, and the csgD, csgE, and csgG are coded by the other operon. These operons are helpful in assembling the curli. The co-expression of curli and cellulose tends to reduce in prevalence as the severity of UTI decreases. This implies that biofilm is associated with ascending UTIs.
S fimbriae is associated with the spread of sepsis, meningitis, and ascending UTIs caused by E. coli. Epithelial and endothelial cells which cover the lower urogenital system and the kidney are attached by UPEC through S fimbriae and F1C fimbriae.,, Fimbrial Dr and Afa adhesins are implicated with UTIs caused by E. coli, particularly with acute gestational pyelonephritis and recurring cystitis.,,, In the kidney, Dr adhesins bind to type IV collagen and decay-accelerating factor causing the development of chronic pyelonephritis. Mutation within the dra region encoding for Dr fimbriae prevents the development of the tubulointerstitial nephritis. UPEC is a flagellated organism which binds to the epithelial cells. Flagellin acts as an invasion for UPEC that cause pyelonephritis by invading the renal collecting duct (CD) cells. UPEC flagella may also enhance the bacterial movement from the bladder to cause infections in the kidney which and could be stopped by UPEC antibodies.
Epidemiological studies show that E. coli strains that express adhesins of the Afa/Dr family are associated with 25%–50% of cystitis in children and 30% of pyelonephritis in pregnant women. Furthermore, strains of E. coli with Dr adhesins have been associated with a two-fold increase in the risk of a recurrent UTI. It has also been shown that UPEC encoding the Dr adhesin could survive for > 1 year within renal tissue. These findings suggest a possible role for Dr/Afa adhesins in recurrent or chronic UTI.,
Bacterial capsule (made up of polysaccharide) covers the bacteria and protects it from the host immune system by escaping phagocytic engulfment and the harmful effects of immune-activated compliments against the bacteria. Gram-negative bacteria cell mostly made up of lipopolysaccharides (LPSs) including E. coli. LPSs are immune activators which induce the production of nitric oxide and cytokine in uncomplicated UTIs. However, the role of LPS in facilitating renal failure and acute allograft injury with ascending UTIs is not well understood.
Bacteria are lysed by a cascade of complement activation system in the human serum. However, UPEC expresses outer membrane proteins, such as traT and Iss, which facilitates the escape of the complement killing. The resistance of E. coli to killing by serum results from the singular or cumulative effects of capsular polysaccharide, O-polysaccharide side chains, and surface proteins. Although the K1 capsule is important in certain strains, other mechanisms appear to be more significant determinants of serum resistance in some populations of E. coli isolates. On the whole, smooth strains are more serum resistant than rough strains and the degree of serum resistance is proportional to the amount of LPS (O antigen) the strain contains. Serum-resistant strains are usually more nephropathogenic than comparable serum-sensitive strains in a variety of models of UTI, even though these resistant strains may not be associated with increased lethality. Summary of uropathogenic Escherichia coli genetic markers and their functions is presented in [Table 1].
|Table 1: Summary of uropathogenic Escherichia coli genetic markers and their functions|
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Bacteria secreted virulence factors
Pathogenic strains of E. coli secrete toxins which are vital virulence factors by causing an inflammatory response.
| Toxins Production|| |
The most virulent secreted toxin by UPEC is α-hemolysin (HlyA) which is encoded by a polycistronic operon, consisting of four genes arranged in the order of hly-CADB. The product of hlyC is important in the activation of the hemolytic toxin (the product of the hlyA gene). The gene products of hlyB and hlyD together with TolC are collectively involved in the secretion of the hemolysin through the bacterial cell wall.
The effects of this toxin in UTIs depend on the concentration secreted by UPEC. At high dosage, HlyA destroys the red blood cells, and the nucleated host cells permeate the UPEC invade the mucosal barriers, damage immune system, and as well enter the nutrients and iron stores of the host.,,, At low dosage, HlyA is able to induce a proinflammatory caspase1/caspase-4-dependent cell death in the bladder. HlyA causes damage and scarring of the kidney, Ca2+ oscillations in the epithelial cells of the renal tubule and the disruption of the normal flow of urine due to ascension and colonization of ureters and kidney parenchyma. These roles of HylA may be unconnected with the adherence properties of UPEC.,,,, HlyA and other toxins produced by E. coli could cause the production of nitric oxide synthase (iNOS) through the extracellular signal-regulated kinase which is independent of the p53 pathway resulting to cell membrane injury and apoptotic cell death.
Hemolytic uropathogenic strains most times also expressPfimbriae. Hemolysin production is usually associated with UPEC strains from patients with pyelonephritis (49%), followed by cystitis isolates and asymptomatic bacteriuria. These data show a significant relationship between hemolysin productions and invasive uropathogenic strains. UPEC strains that produce increased amounts of alpha-hemolysin are also more resistant to the activities of complement in human serum than the nonhemolytic or those with reduced amounts of hemolysin.
Many UPEC strains secrete the cytotoxic necrotizing factor 1 (CNF1) to stimulate in vitro production actin stress fibers and membrane ruffe in a Rho GTPase-dependent manner which permeates E. coli invasion into the kidney cells., However, the extent of the activities of CNF1 in the processes of pyelonephritis associated invasion is not well understood subjecting it to different schools of thoughts. CNF1 produce by UPEC infringes on polymorphonuclear phagocytosis to elicit apoptosis and scarring of the epithelia of the bladder. In a study of Yamamoto et al., 61% of UTI isolates and 38% of bacteremia isolates produced CNF-1 against 10% produced by commensal strains in fecal samples. Of these isolates, approximately 98% that produced CNF-1 also produced hemolysin. Mitsumori et al. reported a CNF-1 prevalence of 64% among patients with UPEC isolates with prostatitis and 36% with pyelonephritis. These results suggest that CNF-1 is associated with increased virulence in UTI pathogenesis. CNF-1 production may also increase the inflammatory response of the host.
Uropathogenic specific protein (Usp) in E. coli is encoded on PAIs together with three downstream small open reading frames (Imu1-3) which are believed to provide immunity to the producer. Usp is more prevalent among UPEC isolates than fecal E. coli isolates from healthy individuals. Several studies have shown various roles for Usp in UTI pathogenesis in different UTI syndromes and patient groups. According to Rijavec et al., there is a significant relationship between Usp and bacteremia of urinary tract origin which is suggestive that Usp is important in the migration of UPEC from the urogenital tract to the bloodstream. Other studies have shown the comparable prevalence of Usp in cystitis, pyelonephritis, and prostatitis isolates. Furthermore, there is an often relationship between Usp and all common serotypes of UPEC.
Outer membrane protease T (OmpT) of E. coli is a surface membrane serine protease that catalyzes the activation of plasminogen to plasmin. OmpT also plays a role in virulence by cleavage of protamine and other cation peptides with antibiotic activity, promoting the persistence of E. coli in the urinary tract.,
UPEC also secrets serine-autotransporter toxin (sat) to intoxicate cell lines of bladder or kidney origin, hence, playing vital activity in UTI pathogenesis., Cytolethal distending toxin (CDT) is another virulence factor in UPEC associated UTIs., Toll/interleukin (IL-1) receptor (TIR) domain-containing protein is a new class of virulence factors which are capable destabilizing TIR signaling to survive during UTIs.
| Iron Upregulation|| |
For UPEC to survive in urinary tract where there is limited iron, UPEC must exhibit its ability to increase the number of receptors on the cell surface of the host (upregulate) required for the acquisition of small-molecule iron chelators called iron-producing siderophores ( Yersinia More Detailsbactin, salmochelin, and aerobactin) to scavenge ferric iron (Fe3+)., The receptors of these siderophores then use a system which has a high affinity for the acquisition of iron called Ton B cytoplasmic membrane-localized complex to bind and chelate iron at the cell surface of the host to enhance ferric iron uptake.
E. coli has gene present in PAIs which encodes proteins for biosynthesis of the yersiniabactin siderophore and its uptake system. One of the important genes residing on the PAIs is fyuA encoding the FyuA (ferric siderophore uptake), which act as a receptor for Fe-yersiniabactin uptake. Hancock and Klemm have reported that the ferric yersiniabactin receptor (FyuA) is required by UPEC for efficient biofilm formation.
Another vital hydroxamate siderophore produced from the condensation of two lysine and one citrate molecules is aerobactin. In UPEC, the aerobactin system is encoded by five sets of genes with four genes encoding the enzymes for aerobactin production and the fifth gene encoding the outer membrane receptor protein., The genes for aerobactin synthesis are named iuc (for iron uptake and chelation) while the receptor gene is iut (for iron uptake and transport). The iuc genes catalyze the biosynthesis of aerobactin through hydroxylation of lysine and acetylation of the hydroxyl group to form hydroxamic acid molecules which react with citrate to form aerobactin.
Studies have shown a relationship between aerobactin system andPfimbriae UPEC isolates from patients with UTI and urosepsis., The aerobactin system is found more commonly among UPEC strains from patients with pyelonephritis (73%), cystitis (49%), or bacteremia (58%) than among patient with asymptomatic bacteriuria patient (38%) and fecal strains (41%). This shows that aerobactin contributes to the virulence E. coli both within and outside of the urinary tract. The association of aerobactin with more serious forms of UTI is seen specifically in infants, girls, and women.,
In order for UPEC to iron during the invasion of the host, salmochelins is produced. This siderophore system is regulated by iroA gene cluster consisting of five genes, iroB, iroC, iroD, iroE, and iroN. iroN gene encodes an outer membrane siderophore receptor which transports different catechol siderophores, including N-(2,3-dihydroxybenzoy)-L-serine and enterochelin; iroB encodes a glucosyltransferase that glucosylates enterobactin; iroC encodes an ABC transporter required for transport of salmochelins; while iroD and iroE encode a cytoplasmic esterase and a periplasmic hydrolase, respectively. [Figure 1] shows the diagram of uropathogenic Escherichia coli-associated fitness and virulence.
|Figure 1: Uropathogenic Escherichia coli-associated fitness and virulence determinants|
Click here to view
| Phylogenetic Evolution of Uropathogenic Escherichia Coli|| |
The strains of the disease-causing and the nondisease E. coli are classified into four main phylogroups groups: A, B1, B2, and D. The basis of this classification into phylogroups is based on inferred evolutionary history through the use of whole-genome sequences to support the phylogenies.,, Studies have shown that ExPEC strains are mostly classified into phylogroup B2 and phylogroup D, while nondisease causing strains are mostly classified into phylogroup A and phylogroup B1. However, due to microbial gene transfer, there is always exchange of virulence genes among phylogroups, which may cause the accommodation of highly virulent strains in phylogroup A and phylogroup B1. This could result to phylogroups containing mixed groups of strains and different clonal populations, thus, creating a more complex scenario in an attempt to establish epidemiological links between phylogroups of E. coli and human infections. However, several reports have shown that phylogroup B2 are predominant among the urine isolates than phylogroup D. This is because isolates of this group carry specialized pathogenic factors, i.e., traits that confer pathogenic potential, which are uncommon between commensal isolates and other E. coli strains which are involved in various extraintestinal infections. These pathogenic factors include adherence characters (depending on the assembly in fimbrial projecting or afimbrial aggregates), toxins genes which code for toxins related to ExPEC strains (mostly displaying cytotoxic necrotizing factor), hemolysin (contributing to destruction of eukaryotic cells), and iron uptake systems.,
The characterization of clonal structure of each phylogroup helps in the recognition of the subsets of clonal groups associated with distinctive clinical signs and symptoms. The recognition of highly virulent ExPEC clones which are universally found such as clones of B2-ST131 and D-ST69 have been facilitated by the development of multilocus sequence typing (MLST) methods and the further classification of the genes into sequence types (STs).,, Molecular analyses of uropathogenic show phylogenetically similarity with the nonpathogenic strains although those pathogenic strains are found in phylogoup B2 and D. Although the uropathogenic strains are capable of causing diarrhea, they are known as pathogenic ExPEC to distinguish them from those causing infections at the gastrointestinal tract.
| Molecular Analysis Used in Assaying Uropathogenic Escherichia Coli Pathogenesis|| |
There are numerous molecular techniques used in investigating the activities of UPEC. The relevance of these techniques on the advancements of research and molecular pathogenesis of UPEC are discussed in this review.
This technique is also known as gene expression profiling. It is the most famous study used in the UPEC molecular studies. This is a process where DNA transcription produces RNA, and RNA translation produces proteins. This method measures genes which are expressed in a cell at any point in time.
This is a technique where there is a transfer of transposons (genes which are able to change position in a single cell) to the chromosomes of the host cells in order for the function of an extant gene on the chromosome to be interrupted or modified resulting to mutation. In transposon mutagenesis, signature-tagged mutagenesis (STM) is specifically used. The used of STM murine model has been employed in the identification of genes of interest which has helped in the discovery of new and existing virulence factors of UPEC-associated UTIs.
Transposon site hybridization and transposon insertion site sequencing are improved systems of STM. Transposon insertion libraries are made up of genome-saturating numbers of transposon mutants which undergo selection depending on the condition of interest. The frequency of this transposon insertion is detected and determined by sequencing the DNA genome at a given locus. In these systems, the insignificant represented mutants in terms of out pool and in-pool comparison are characterized as putative virulence or fitness genes, and their roles in fitness or virulence could be ascertained by further characterization of the mutants.
The foundation of this technology is the hybridization based-detection of complementary DNA (cDNA). The relative abundance of a set of transcribed genes is used to determine upregulated or downregulated genes of interest in a given condition. The determination of absolute quantity of these transcribed genes could also be done using specialized assemblages such as gene chip (Affymetrix). Comparative genomic-hybridization studies for analysis of gene content could also be done using DNA microarrays. This molecular process has transformed the capability to reveal a universal outlook on UPEC gene expression under a given conditions even though RNA-seq (a sequencing-based technique) is gradually overtaking the DNA-microarray.,,,
This involves the use of high-throughput sequencing platforms such as Illumina in massively parallel sequencing of cDNA libraries utilizing. Both absolute and differential expressions under various conditions can be evaluated using RNA-seq. RNA-seq is used in global analysis in an unbiased manner at a hitherto unprecedented resolution and dynamic range over DNA microarrays. Regions of the transcripts, promoter regions, novel transcripts, including small regulatory RNAs, and operon structure which were not translated in DNA microarrays can be characterized using RNA-seq.
Transposon-directed insertion-site sequencing
In mouse model, serum resistance and zebrafish model, transposon-directed insertion-site sequencing have been used to identify the genetic determinants of fitness in UPEC during bacteremia which has the potential to explain the unrecognized fitness and virulence mechanisms involved in the molecular pathogenesis of UPEC.,,
This is also called high-throughput or massively parallel sequencing, is a genre of technologies that allows for the simultaneous and independent sequencing of many (thousands to billion) DNA fragments. The applications of next-generation sequencing (NGS) in clinical microbiological testing allow for an unbiased approach to the detection of pathogens. This applies to sequence of genomes, resequencing of genomes, transcriptome profiling (RNA-Seq), DNA-protein interactions (chromatin immunoprecipitation-sequencing) and epigenome characterization. Resequencing is necessary because the genome of a single individual of a species will not indicate all of the genome variations among other individuals of the same species.
Messerer et al. sequenced for the first time in large scale the whole genomes of the Escherichia coli reference collection and some additional strains with NGS establish the link between horizontal gene transfer and its impact evolution of Escherichia coli reference collection. PAIs encode several virulence factors such as adhesins, toxins, capsules, and siderophore systems and play significant roles in the evolution of pathogenic bacteria such as extraintestinal pathogenic Escherichia coli (ExPEC) which are responsible for pyelonephritis, cystitis, septicemia, and newborn meningitis.
With the indiscriminate use of antibiotics and emergence of multidrug-resistant organisms due to extended-spectrum beta-lactamase (ESBL) production which have led to high global mortality and morbidity rate, NGS is a vital advancement in an effort to comprehensively characterizing antimicrobial-resistant bacteria and exploring different β-lactamase resistance mechanisms and phylogenetic linkage among ESBL-positive isolates of E. coli.,,,
High-resolution liquid chromatography-mass spectrometry/mass spectrometry
This is used as an alternative method to gel electrophoresis for visualizing fragments of DNA where DNA fragments generated by chain-termination sequencing reactions are compared by mass rather than by size. Each nucleotide has a different mass, and this difference is done by mass spectrometry (MS). Single-nucleotide mutations in a fragment can be more easily detected using MS than using gel electrophoresis. Matrix-assisted laser desorption/ionization time-of-flight MS detects differences between RNA fragments more easily; thus, researchers may indirectly sequence DNA with MS-based methods by first converting it to RNA.
| Concluding Remarks|| |
UPEC are very unique strains of E. coli which have the tendencies to colonize and cause infections in the urinary tracts of humans. Diverse virulence factors have been discovered as playing vital roles in the UTIs caused by UPEC. The roles of these virulence factors are not individually but in a combined state. The virulence factors of UPEC enable the organisms to advance from gastrointestinal tract to urinary tract to cause disease, hence, the basis for their classification as extraintestinal organisms.
Phylogenetic studies have further established that the UPEC pathotypes, commensal strains, and other gastrointestinal pathotypes are grouped into four phylogroups. The UPEC strains are found in phylogroup B and D. However, most pathotypes associated with UTIs are found in phylogroup B. They are responsible for majority of the UTIs and recurrent UTIs, particularly in women. The understanding of molecular procedures in the genomics of UPEC will lead to further studies on the roles of UPEC in UTIs, particularly to the emergence of new genes.
Special thanks to Mr. Solomon Ben for his contributions to this review.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Yan F, Polk DB. Commensal bacteria in the gut: Learning who our friends are. Curr Opin Gastroenterol 2004;20:565-71.
Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli
. Nat Rev Microbiol 2004;2:123-40.
Wiles TJ, Kulesus RR, Mulvey MA. Origins and virulence mechanisms of uropathogenic Escherichia coli
. Exp Mol Pathol 2008;85:11-9.
Bergsten G, Wullt B, Svanborg C. Escherichia coli
, fimbriae, bacterial persistence and host response induction in the human urinary tract. Int J Med Microbiol 2005;295:487-502.
Lloyd AL, Rasko DA, Mobley HL. Defining genomic islands and uropathogen-specific genes in uropathogenic Escherichia coli
. J Bacteriol 2007;189:3532-46.
Foxman B. Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. Dis Mon 2003;49:53-70.
Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 1997;11:551-81.
Svanborg C, Godaly G. Bacterial virulence in urinary tract infection. Infect Dis Clin North Am 1997;11:513-29.
Sadler I, Chiang A, Kurihara T, Rothblatt J, Way J, Silver P, et al
. A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to dnaJ, an Escherichia coli
heat shock protein. J Cell Biol 1989;109:2665-75.
Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, et al.
Induction and evasion of host defenses by Type 1-piliated uropathogenic Escherichia coli
. Science 1998;282:1494-7.
Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J 2000;19:2803-12.
Kaijser B, Ahlstedt S. Protective capacity of antibodies against Escherichia coli
and K antigens. Infect Immun 1977;17:286-9.
Edén CS, Hanson LA, Jodal U, Lindberg U, Akerlund AS. Variable adherence to normal human urinary-tract epithelial cells of Escherichia coli
strains associated with various forms of urinary-tract infection. Lancet 1976;1:490-2.
Lindberg U, Hanson LA, Jodal U, Lidin-Janson G, Lincoln K, Olling S, et al.
Asymptomatic bacteriuria in schoolgirls. II. Differences in Escherichia coli
causing asymptomatic bacteriuria. Acta Paediatr Scand 1975;64:432-6.
Oelschlaeger TA, Dobrindt U, Hacker J. Pathogenicity islands of uropathogenic E. coli
and the evolution of virulence. Int J Antimicrob Agents 2002;19:517-21.
Emody L, Kerényi M, Nagy G. Virulence factors of uropathogenic Escherichia coli
. Int J Antimicrob Agents 2003;22 Suppl 2:29-33.
Mulvey MA. Adhesion and entry of uropathogenic Escherichia coli
. Cell Microbiol 2002;4:257-71.
Bergsten G, Wullt B, Schembri MA, Leijonhufvud I, Svanborg C. Do Type 1 fimbriae promote inflammation in the human urinary tract? Cell Microbiol 2007;9:1766-81.
Snyder JA, Haugen BJ, Buckles EL, Lockatell CV, Johnson DE, Donnenberg MS, et al.
Transcriptome of uropathogenic Escherichia coli
during urinary tract infection. Infect Immun 2004;72:6373-81.
Connell I, Agace W, Klemm P, Schembri M, Mărild S, Svanborg C, et al.
Type 1 fimbrial expression enhances Escherichia coli
virulence for the urinary tract. Proc Natl Acad Sci U S A 1996;93:9827-32.
Hultgren SJ, Porter TN, Schaeffer AJ, Duncan JL. Role of type 1 pili and effects of phase variation on lower urinary tract infections produced by Escherichia coli
. Infect Immun 1985;50:370-7.
Hagberg L, Engberg I, Freter R, Lam J, Olling S, Svanborg Edén C, et al.
Ascending, unobstructed urinary tract infection in mice caused by pyelonephritogenic Escherichia coli
of human origin. Infect Immun 1983;40:273-83.
Hagberg L, Jodal U, Korhonen TK, Lidin-Janson G, Lindberg U, Svanborg Edén C, et al.
Adhesion, hemagglutination, and virulence of Escherichia coli
causing urinary tract infections. Infect Immun 1981;31:564-70.
Duguid JP, Old D. Adhesive properties of Enterobacteriaceae
. In: Beachey E, editor. Bacterial Adherence, Receptors and Recognition. London, UK: Chapman and Hall; 1980. p. 185-217.
Plos K, Lomberg H, Hull S, Johansson I, Svanborg C. Escherichia coli
in patients with renal scarring: Genotype and phenotype of gal alpha 1-4Gal beta-, forssman- and mannose-specific adhesins. Pediatr Infect Dis J 1991;10:15-9.
Thumbikat P, Berry RE, Zhou G, Billips BK, Yaggie RE, Zaichuk T, et al.
Bacteria-induced uroplakin signaling mediates bladder response to infection. PLoS Pathog 2009;5:e1000415.
Bates JM, Raffi HM, Prasadan K, Mascarenhas R, Laszik Z, Maeda N, et al.
Tamm-horsfall protein knockout mice are more prone to urinary tract infection: Rapid communication. Kidney Int 2004;65:791-7.
Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR. Tamm-horsfall protein binds to type 1 fimbriated Escherichia coli
and prevents E. coli
from binding to uroplakin ia and ib receptors. J Biol Chem 2001;276:9924-30.
Soto SM. Importance of biofilms in urinary tract infections: New therapeutic approaches. Adv Biol 2014;2014:1-13.
Pereira AL, Silva TN, Gomes AC, Araújo AC, Giugliano LG. Diarrhea-associated biofilm formed by enteroaggregative Escherichia coli
and aggregative Citrobacter freundii
: A consortium mediated by putative F
pili. BMC Microbiol 2010;10:57.
Ott M, Hacker J, Schmoll T, Jarchau T, Korhonen TK, Goebel W, et al
. Analysis of the genetic determinants coding for the S-fimbrial adhesin (sfa) in different Escherichia coli
strains causing meningitis or urinary tract infections. Infect Immun 1986;54:646-53.
Opal SM, Cross AS, Gemski P, Lyhte LW. Aerobactin and alpha-hemolysin as virulence determinants in Escherichia coli
isolated from human blood, urine, and stool. J Infect Dis 1990;161:794-6.
Johnson JR, Roberts PL, Stamm WE.P
fimbriae and other virulence factors in Escherichia coli
urosepsis: Association with patients' characteristics. J Infect Dis 1987;156:225-9.
Godaly G, Bergsten G, Frendéus B, Hang L, Hedlund M, Karpman D, et al.
Innate defences and resistance to gram negative mucosal infection. Adv Exp Med Biol 2000;485:9-24.
Hedlund M, Wachtler C, Johansson E, Hang L, Somerville JE, Darveau RP, et al.
fimbriae-dependent, lipopolysaccharide-independent activation of epithelial cytokine responses. Mol Microbiol 1999;33:693-703.
Leffler H, Eden CS. Chemical identification of a glycosphingolipid receptor for Escherichia coli
attaching to human urinary tract epithelial cells and agglutinating human erythrocytes. FEMS Microbiol Lett 1980;8:127-34.
Leffler H, Svanborg-Edén C. Glycolipid receptors for uropathogenic Escherichia coli
on human erythrocytes and uroepithelial cells. Infect Immun 1981;34:920-9.
Väisänen V, Elo J, Tallgren LG, Siitonen A, Mäkelä PH, Svanborg-Edén C, et al.
Mannose-resistant haemagglutination and P
antigen recognition are characteristic of Escherichia coli
causing primary pyelonephritis. Lancet 1981;2:1366-9.
Plos K, Connell H, Jodal U, Marklund BI, Mårild S, Wettergren B, et al.
Intestinal carriage of P
fimbriated Escherichia coli
and the susceptibility to urinary tract infection in young children. J Infect Dis 1995;171:625-31.
Hull RA, Gill RE, Hsu P, Minshew BH, Falkow S. Construction and expression of recombinant plasmids encoding type 1 or D-mannose-resistant pili from a urinary tract infection Escherichia coli
isolate. Infect Immun 1981;33:933-8.
Wullt B, Bergsten G, Connell H, Röllano P, Gebretsadik N, Hull R, et al.
fimbriae enhance the early establishment of Escherichia coli
in the human urinary tract. Mol Microbiol 2000;38:456-64.
Fischer H, Ellström P, Ekström K, Gustafsson L, Gustafsson M, Svanborg C, et al
. Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4. Cell Microbiol 2007;9:1239-51.
Melican K, Sandoval RM, Kader A, Josefsson L, Tanner GA, Molitoris BA, et al.
Uropathogenic Escherichia coli P
and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction. PLoS Pathog 2011;7:e1001298.
Stærk K, Khandige S, Kolmos HJ, Møller-Jensen J, Andersen TE. Uropathogenic Escherichia coli
express Type 1 fimbriae only in surface adherent populations under physiological growth conditions. J Infect Dis 2016;213:386-94.
Kai-Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, et al.
Uropathogenic Escherichia coli
modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathog 2010;6:e1001010.
Kostakioti M, Hadjifrangiskou M, Hultgren SJ. Bacterial biofilms: Development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med 2013;3:a10306.
de la Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE. Bacterial biofilm development as a multicellular adaptation: Antibiotic resistance and new therapeutic strategies. Curr Opin Microbiol 2013;16:580-9.
Lüthje P, Brauner A. Ag43 promotes persistence of uropathogenic Escherichia coli
isolates in the urinary tract. J Clin Microbiol 2010;48:2316-7.
Schroeder M, Brooks BD, Brooks AE. The complex relationship between virulence and antibiotic resistance. Genes (Basel) 2017;8:39.
Gophna U, Barlev M, Seijffers R, Oelschlager TA, Hacker J, Ron EZ, et al.
Curli fibers mediate internalization of Escherichia coli
by eukaryotic cells. Infect Immun 2001;69:2659-65.
Hacker JS, Morschhauser J. In: Klemm P, editor. Fimbriae, Adhesion, Genetics, Biogenesis, and Vaccines. Boca Raton, Fla, USA: CRC Press; 1994. p. 27-36.
Marre R, Kreft B, Hacker J. Genetically engineered S and F1C fimbriae differ in their contribution to adherence of Escherichia coli
to cultured renal tubular cells. Infect Immun 1990;58:3434-7.
Servin AL. Pathogenesis of human diffusely adhering Escherichia coli
expressing afa/Dr adhesins (Afa/Dr DAEC): Current insights and future challenges. Clin Microbiol Rev 2014;27:823-69.
Garcia MI, Gounon P, Courcoux P, Labigne A, Le Bouguenec C. The afimbrial adhesive sheath encoded by the afa-3 gene cluster of pathogenic Escherichia coli
is composed of two adhesins. Mol Microbiol 1996;19:683-93.
Foxman B, Zhang L, Tallman P, Palin K, Rode C, Bloch C, et al.
Virulence characteristics of escherichia coli
causing first urinary tract infection predict risk of second infection. J Infect Dis 1995;172:1536-41.
Nowicki B, Labigne A, Moseley S, Hull R, Hull S, Moulds J, et al
. The dr hemagglutinin, afimbrial adhesins AFA-I and AFA-III, and F1845 fimbriae of uropathogenic and diarrhea-associated Escherichia coli
belong to a family of hemagglutinins with dr receptor recognition. Infect Immun 1990;58:279-81.
Nowicki B, Selvarangan R, Nowicki S. Family of Escherichia coli
Dr Adhesins: Decay-accelerating factor receptor recognition and invasiveness. J Infect Dis 2001;183 Suppl 1:S24-7.
Goluszko P, Moseley SL, Truong LD, Kaul A, Williford JR, Selvarangan R, et al
. Development of experimental model of chronic pyelonephritis with Escherichia coli
O75: K5: H-bearing Dr fimbriae: Mutation in the dra region prevented tubulointerstitial nephritis. J Clin Invest 1997;99:1662-72.
Pichon C, Héchard C, du Merle L, Chaudray C, Bonne I, Guadagnini S, et al.
Uropathogenic Escherichia coli
AL511 requires flagellum to enter renal collecting duct cells. Cell Microbiol 2009;11:616-28.
Schwan WR. Flagella allow uropathogenic Escherichia coli
ascension into murine kidneys. Int J Med Microbiol 2008;298:441-7.
Servin AL. Pathogenesis of Afa/Dr diffusely adhering Escherichia coli
. Clin Microbiol Rev 2005;18:264-92.
Salyers AA, Whitt DD. Bacterial Pathogenesis: Molecular Approach. Washington DC, USA: ASM Press; 2002.
Johnson JR. Virulence factors in Escherichia coli
urinary tract infection. Clin Microbiol Rev 1991;4:80-128.
Cunningham PN, Wang Y, Guo R, He G, Quigg RJ. Role of toll-like receptor 4 in endotoxin-induced acute renal failure. J Immunol 2004;172:2629-35.
Elliott SJ, Srinivas S, Albert MJ, Alam K, Robins-Browne RM, Gunzburg ST, et al.
Characterization of the roles of hemolysin and other toxins in enteropathy caused by alpha-hemolytic Escherichia coli
linked to human diarrhea. Infect Immun 1998;66:2040-51.
Montenegro MA, Bitter-Suermann D, Timmis JK, Agüero ME, Cabello FC, Sanyal SC, et al.
TraT gene sequences, serum resistance and pathogenicity-related factors in clinical isolates of Escherichia coli
and other gram-negative bacteria. J Gen Microbiol 1985;131:1511-21.
Timmis KN, Boulnois GJ, Bitter-Suermann D, Cabello FC. Surface components of Escherichia coli
that mediate resistance to the bactericidal activities of serum and phagocytes. Curr Top Microbiol Immunol 1985;118:197-218.
Goldman RC, Joiner K, Leive L. Serum-resistant mutants of Escherichia coli
O111 contain increased lipopolysaccharide, lack an O antigen-containing capsule, and cover more of their lipid A core with O antigen. J Bacteriol 1984;159:877-82.
Domingue GJ, Laucirica R, Baliga P, Covington S, Robledo JA, Li SC, et al.
Virulence of wild-type E. Coli uroisolates in experimental pyelonephritis. Kidney Int 1988;34:761-5.
Iwahi T, Abe Y, Tsuchiya K. Virulence of Escherichia coli
in ascending urinary-tract infection in mice. J Med Microbiol 1982;15:303-16.
Cavalieri SJ, Bohach GA, Snyder IS. Escherichia coli
alpha-hemolysin: Characteristics and probable role in pathogenicity. Microbiol Rev 1984;48:326-43.
Cirl C, Wieser A, Yadav M, Duerr S, Schubert S, Fischer H, et al.
Subversion of toll-like receptor signaling by a unique family of bacterial toll/interleukin-1 receptor domain-containing proteins. Nat Med 2008;14:399-406.
Laestadius A, Richter-Dahlfors A, Aperia A. Dual effects of Escherichia coli
alpha-hemolysin on rat renal proximal tubule cells. Kidney Int 2002;62:2035-42.
Keane WF, Welch R, Gekker G, Peterson PK. Mechanism of Escherichia coli
alpha-hemolysin-induced injury to isolated renal tubular cells. Am J Pathol 1987;126:350-7.
Uhlén P, Laestadius A, Jahnukainen T, Söderblom T, Bäckhed F, Celsi G, et al
. Alpha-haemolysin of uropathogenic E. coli
induces ca2+ oscillations in renal epithelial cells. Nature 2000;405:694-7.
Kohan DE. Role of endothelin and tumour necrosis factor in the renal response to sepsis. Nephrol Dial Transplant 1994;9 Suppl 4:73-7.
Jakobsson B, Berg U, Svensson L. Renal scarring after acute pyelonephritis. Arch Dis Child 1994;70:111-5.
Ditchfield MR, de Campo JF, Nolan TM, Cook DJ, Grimwood K, Powell HR, et al.
Risk factors in the development of early renal cortical defects in children with urinary tract infection. AJR Am J Roentgenol 1994;162:1393-7.
Mobley HL, Green DM, Trifillis AL, Johnson DE, Chippendale GR, Lockatell CV, et al.
Pyelonephritogenic Escherichia coli
and killing of cultured human renal proximal tubular epithelial cells: Role of hemolysin in some strains. Infect Immun 1990;58:1281-9.
Chen M, Jahnukainen T, Bao W, Daré E, Ceccatelli S, Celsi G, et al.
Uropathogenic Escherichia coli
toxins induce caspase-independent apoptosis in renal proximal tubular cells via ERK signaling. Am J Nephrol 2003;23:140-51.
Czirók E, Milch H, Csiszár K, Csik M. Virulence factors of escherichia coli
. III. Correlation with Escherichia coli
pathogenicity of haemolysin production, haemagglutinating capacity, antigens K1, K5, and colicinogenicity. Acta Microbiol Hung 1986;33:69-83.
Marrs CF, Zhang L, Foxman B. Escherichia coli
mediated urinary tract infections: Are there distinct uropathogenic E
(UPEC) pathotypes? FEMS Microbiol Lett 2005;252:183-90.
Birosová E, Siegfried L, Kmet'ová M, Makara A, Ostró A, Gresová A, et al.
Detection of virulence factors in alpha-haemolytic Escherichia coli
strains isolated from various clinical materials. Clin Microbiol Infect 2004;10:569-73.
Landraud L, Gauthier M, Fosse T, Boquet P. Frequency of Escherichia coli
strains producing the cytotoxic necrotizing factor (CNF1) in nosocomial urinary tract infections. Lett Appl Microbiol 2000;30:213-6.
De Rycke J, Milon A, Oswald E. Necrotoxic Escherichia coli
(NTEC): Two emerging categories of human and animal pathogens. Vet Res 1999;30:221-33.
Chen M, Tofighi R, Bao W, Aspevall O, Jahnukainen T, Gustafsson LE, et al.
Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli
toxins. Pediatr Nephrol 2006;21:382-9.
Bower JM, Eto DS, Mulvey MA. Covert operations of uropathogenic Escherichia coli
within the urinary tract. Traffic 2005;6:18-31.
Yamamoto S, Terai A, Yuri K, Kurazono H, Takeda Y, Yoshida O, et al.
Detection of urovirulence factors in Escherichia coli
by multiplex polymerase chain reaction. FEMS Immunol Med Microbiol 1995;12:85-90.
Mitsumori K, Terai A, Yamamoto S, Ishitoya S, Yoshida O. Virulence characteristics of Escherichia coli
in acute bacterial prostatitis. J Infect Dis 1999;180:1378-81.
Kanamaru S, Kurazono H, Ishitoya S, Terai A, Habuchi T, Nakano M, et al.
Distribution and genetic association of putative uropathogenic virulence factors iroN, iha, kpsMT, OmpT and USP in Escherichia coli
isolated from urinary tract infections in Japan. J Urol 2003;170:2490-3.
Rijavec M, Müller-Premru M, Zakotnik B, Zgur-Bertok D. Virulence factors and biofilm production among Escherichia coli
strains causing bacteraemia of urinary tract origin. J Med Microbiol 2008;57:1329-34.
Kanamaru S, Kurazono H, Nakano M, Terai A, Ogawa O, Yamamoto S, et al.
Subtyping of uropathogenic Escherichia coli
according to the pathogenicity island encoding uropathogenic-specific protein: Comparison with phylogenetic groups. Int J Urol 2006;13:754-60.
Yamamoto S. Molecular epidemiology of uropathogenic Escherichia coli
. J Infect Chemother 2007;13:68-73.
Hui CY, Guo Y, He QS, Peng L, Wu SC, Cao H, et al. Escherichia coli
outer membrane protease OmpT confers resistance to urinary cationic peptides. Microbiol Immunol 2010;54:452-9.
Guina T, Yi EC, Wang H, Hackett M, Miller SI. A phoP-regulated outer membrane protease of Salmonella enterica
serovar Typhimurium promotes resistance to alpha-helical antimicrobial peptides. J Bacteriol 2000;182:4077-86.
Stumpe S, Schmid R, Stephens DL, Georgiou G, Bakker EP. Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing cells of Escherichia coli
. J Bacteriol 1998;180:4002-6.
Guyer DM, Radulovic S, Jones FE, Mobley HL. Sat, the secreted autotransporter toxin of uropathogenic Escherichia coli
, is a vacuolating cytotoxin for bladder and kidney epithelial cells. Infect Immun 2002;70:4539-46.
Guyer DM, Henderson IR, Nataro JP, Mobley HL. Identification of sat, an autotransporter toxin produced by uropathogenic Escherichia coli
. Mol Microbiol 2000;38:53-66.
Féria CP, Correia JD, Gonçalves J, Machado J. Detection of virulence factors in uropathogenic Escherichia coli
isolated from humans, dogs and cats in Portugal. Adv Exp Med Biol 2000;485:305-8.
Tóth I, Hérault F, Beutin L, Oswald E. Production of cytolethal distending toxins by pathogenic Escherichia coli
strains isolated from human and animal sources: Establishment of the existence of a new cdt variant (Type IV). J Clin Microbiol 2003;41:4285-91.
Reigstad CS, Hultgren SJ, Gordon JI. Functional genomic studies of uropathogenic Escherichia coli
and host urothelial cells when intracellular bacterial communities are assembled. J Biol Chem 2007;282:21259-67.
Skaar EP. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog 2010;6:e1000949.
O'Brien VP, Hannan TJ, Nielsen HV, Hultgren SJ. Drug and vaccine development for the treatment and prevention of urinary tract infections. Microbiol Spectr 2016;4:42.
Schubert S, Rakin A, Heesemann J. The yersinia high-pathogenicity island (HPI): Evolutionary and functional aspects. Int J Med Microbiol 2004;294:83-94.
Schubert S, Picard B, Gouriou S, Heesemann J, Denamur E. Yersinia high-pathogenicity island contributes to virulence in Escherichia coli
causing extraintestinal infections. Infect Immun 2002;70:5335-7.
Hancock V, Klemm P. Global gene expression profiling of asymptomatic bacteriuria Escherichia coli
during biofilm growth in human urine. Infect Immun 2007;75:966-76.
Carbonetti NH, Boonchai S, Parry SH, Väisänen-Rhen V, Korhonen TK, Williams PH, et al.
Aerobactin-mediated iron uptake by Escherichia coli
isolates from human extraintestinal infections. Infect Immun 1986;51:966-8.
Crosa JH. Genetics and molecular biology of siderophore-mediated iron transport in bacteria. Microbiol Rev 1989;53:517-30.
de Lorenzo V, Bindereif A, Paw BH, Neilands JB. Aerobactin biosynthesis and transport genes of plasmid colV-K30 in Escherichia coli
K-12. J Bacteriol 1986;165:570-8.
Jacobson SH, Hammarlind M, Lidefeldt KJ, Osterberg E, Tullus K, Brauner A, et al.
Incidence of aerobactin-positive Escherichia coli
strains in patients with symptomatic urinary tract infection. Eur J Clin Microbiol Infect Dis 1988;7:630-4.
Colonna B, Nicoletti M, Visca P, Casalino M, Valenti P, Maimone F, et al.
Composite IS1 elements encoding hydroxamate-mediated iron uptake in FIme plasmids from epidemic salmonella spp. J Bacteriol 1985;162:307-16.
Ruiz J, Simon K, Horcajada JP, Velasco M, Barranco M, Roig G, et al
. Differences in virulence factors among clinical isolates of Escherichia coli
causing cystitis and pyelonephritis in women and prostatitis in men. J Clin Microbiol 2002;40:4445-9.
Caza M, Lépine F, Milot S, Dozois CM. Specific roles of the iroBCDEN genes in virulence of an avian pathogenic Escherichia coli
O78 strain and in production of salmochelins. Infect Immun 2008;76:3539-49.
Barber AE, Norton JP, Wiles TJ, Mulvey MA. Strengths and limitations of model systems for the study of urinary tract infections and related pathologies. Microbiol Mol Biol Rev 2016;80:351-67.
Doumith M, Day MJ, Hope R, Wain J, Woodford N. Improved multiplex PCR strategy for rapid assignment of the four major Escherichia coli
phylogenetic groups. J Clin Microbiol 2012;50:3108-10.
Meier-Kolthoff JP, Hahnke RL, Petersen J, Scheuner C, Michael V, Fiebig A, et al
. Complete genome sequence of DSM 30083(T), the type strain (U5/41(T)) of Escherichia coli
, and a proposal for delineating subspecies in microbial taxonomy. Stand Genomic Sci 2014;9:2.
Sims GE, Kim SH. Whole-genome phylogeny of Escherichia coli/Shigella group by feature frequency profiles (FFPs). Proc Natl Acad Sci U S A 2011;108:8329-34.
Brzuszkiewicz E, Thürmer A, Schuldes J, Leimbach A, Liesegang H, Meyer FD, et al
. Genome sequence analyses of two isolates from the recent Escherichia coli
outbreak in Germany reveal the emergence of a new pathotype: Entero-aggregative-haemorrhagic Escherichia coli
(EAHEC). Arch Microbiol 2011;193:883-91.
Dias RC, Marangoni DV, Smith SP, Alves EM, Pellegrino FL, Riley LW, et al
. Clonal composition of Escherichia coli
causing community-acquired urinary tract infections in the state of Rio de Janeiro, Brazil. Microb Drug Resist 2009;15:303-8.
Peerayeh SN, Navidinia M, Fallah F, Bakhshi B, Jamali J. Pathogenicity determinants and epidemiology of uropathogenic E. coli
(UPEC) strains isolated from children with urinary tract infection (UTI) to define distinct pathotypes. Biomed Res 2018;29:2035-43.
Johnson JR, Scheutz F, Ulleryd P, Kuskowski MA, O'Bryan TT, Sandberg T, et al
. Phylogenetic and pathotypic comparison of concurrent urine and rectal Escherichia coli
isolates from men with febrile urinary tract infection. J Clin Microbiol 2005;43:3895-900.
Blanco J, Mora A, Mamani R, López C, Blanco M, Dahbi G, et al
. National survey of Escherichia coli
causing extraintestinal infections reveals the spread of drug-resistant clonal groups O25b: H4-B2-ST131, O15: H1-D-ST393 and CGA-D-ST69 with high virulence gene content in Spain. J Antimicrob Chemother 2011;66:2011-21.
Nicolas-Chanoine MH, Bertrand X, Madec JY. Escherichia coli
ST131, an intriguing clonal group. Clin Microbiol Rev 2014;27:543-74.
Petty NK, Ben Zakour NL, Stanton-Cook M, Skippington E, Totsika M, Forde BM, et al.
Global dissemination of a multidrug resistant Escherichia coli
clone. Proc Natl Acad Sci U S A 2014;111:5694-9.
Russo TA, Johnson JR. Proposal for a new inclusive designation for extraintestinal pathogenic isolates of Escherichia coli
: ExPEC. J Infect Dis 2000;181:1753-4.
Crick F. Central dogma of molecular biology. Nature 1970;227:561-3.
Metsis A, Andersson U, Baurén G, Ernfors P, Lönnerberg P, Montelius A, et al.
Whole-genome expression profiling through fragment display and combinatorial gene identification. Nucleic Acids Res 2004;32:e127.
Skipper KA, Andersen PR, Sharma N, Mikkelsen JG. DNA transposon-based gene vehicles scenes from an evolutionary drive. J Biomed Sci 2013;20:92.
Bahrani-Mougeot FK, Buckles EL, Lockatell CV, Hebel JR, Johnson DE, Tang CM, et al.
Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic Escherichia coli
virulence determinants in the murine urinary tract. Mol Microbiol 2002;45:1079-93.
Hagan EC, Lloyd AL, Rasko DA, Faerber GJ, Mobley HL. Escherichia coli
global gene expression in urine from women with urinary tract infection. PLoS Pathog 2010;6:e1001187.
Hancock V, Seshasayee AS, Ussery DW, Luscombe NM, Klemm P. Transcriptomics and adaptive genomics of the asymptomatic bacteriuria Escherichia coli
strain 83972. Mol Genet Genomics 2008;279:523-34.
Güell M, Yus E, Lluch-Senar M, Serrano L. Bacterial transcriptomics: What is beyond the RNA horiz-ome? Nat Rev Microbiol 2011;9:658-69.
Subashchandrabose S, Smith SN, Spurbeck RR, Kole MM, Mobley HL. Genome-wide detection of fitness genes in uropathogenic Escherichia coli
during systemic infection. PLoS Pathog 2013;9:e1003788.
Phan MD, Peters KM, Sarkar S, Lukowski SW, Allsopp LP, Gomes Moriel D, et al.
The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli
clone. PLoS Genet 2013;9:e1003834.
Wiles TJ, Norton JP, Russell CW, Dalley BK, Fischer KF, Mulvey MA, et al.
Combining quantitative genetic footprinting and trait enrichment analysis to identify fitness determinants of a bacterial pathogen. PLoS Genet 2013;9:e1003716.
de Magalhães JP, Finch CE, Janssens G. Next-generation sequencing in aging research: Emerging applications, problems, pitfalls and possible solutions. Ageing Res Rev 2010;9:315-23.
Messerer M, Fischer W, Schubert S. Investigation of horizontal gene transfer of pathogenicity islands in Escherichia coli
using next-generation sequencing. PLoS One 2017;12:e179880.
Clermont O, Bonacorsi S, Bingen E. Rapid and simple determination of the escherichia coli
phylogenetic group. Appl Environ Microbiol 2000;66:4555-8.
Mehrad B, Clark NM, Zhanel GG, Lynch JP 3rd
. Antimicrobial resistance in hospital-acquired gram-negative bacterial infections. Chest 2015;147:1413-21.
Tang SS, Apisarnthanarak A, Hsu LY. Mechanisms of β-lactam antimicrobial resistance and epidemiology of major community- and healthcare-associated multidrug-resistant bacteria. Adv Drug Deliv Rev 2014;78:3-13.
Ghafourian S, Sadeghifard N, Soheili S, Sekawi Z. Extended spectrum beta-lactamases: Definition, classification and epidemiology. Curr Issues Mol Biol 2015;17:11-21.
Sherry NL, Porter JL, Seemann T, Watkins A, Stinear TP, Howden BP, et al.
Outbreak investigation using high-throughput genome sequencing within a diagnostic microbiology laboratory. J Clin Microbiol 2013;51:1396-401.
Edwards JR, Ruparel H, Ju J. Mass-spectrometry DNA sequencing. Mutat Res 2005;573:3-12.