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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 13-22

Virulence markers, phylogenetic evolution, and molecular techniques of uropathogenic Escherichia coli


Department of Medical Laboratory Science, University of Calabar, Calabar, Nigeria

Date of Submission17-Jul-2019
Date of Decision17-Aug-2019
Date of Acceptance27-Aug-2019
Date of Web Publication06-Jan-2020

Correspondence Address:
Etefia U Etefia
Department of Medical Laboratory Science, University of Calabar, Calabar
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JNSM.JNSM_31_19

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  Abstract 


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 2020 Apr 2];3:13-22. Available from: http://www.jnsmonline.org/text.asp?2020/3/1/13/269240




  Introduction Top


 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.[1] However, in the immunosuppressed individuals or a violated gastrointestinal environment, these strains E. coli which do not cause disease, could become pathogenic.[2] 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.[2]

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.[3]

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.[4],[5] 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.[6],[7],[8],[9]

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.[10],[11] 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.[12],[13],[14]

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 Top


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).[3],[15] Virulence factors of UPEC are classified into two categories: (i) bacterial cell surface virulence factors and (ii) bacteria secreted virulence factors.[16]

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.[17] 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.[17]


  Adhesins and Biofilms Production Top


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.[18],[19],[20],[21],[22],[23],[24] According to Plos et al.,[25] 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.[11] 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.[3],[11],[26] 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.[27],[28]

Although most studies have confirmed that type 1 fimbriae play a vital role in the colonization of bladder colonization by UPEC,[29],[30] 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%.[31] However, in contrast, the level of expression of type 1 fimbriae among UPEC blood isolates (81%) is significantly different from that of fecal strains.[32],[33]

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.[34],[35],[36],[37],[38],[39]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.[2],[40],[41] This binding produces ceramide which antagonizes Toll-like receptor 4 resulting in the development of UTIs associated inflammation and pain.[4],[42] 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.[43]

According to Soto,[29] 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.[29] 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.[44]

Biofilm production by E. coli is important in determining its virulence factor by contributing to the bacterial resistance.[45],[46],[47],[48],[49] 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.[45],[46],[47] 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.[50] 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.[45]

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.[12],[51],[52] Fimbrial Dr and Afa adhesins are implicated with UTIs caused by E. coli, particularly with acute gestational pyelonephritis and recurring cystitis.[53],[54],[55],[56] In the kidney, Dr adhesins bind to type IV collagen and decay-accelerating factor causing the development of chronic pyelonephritis.[57] Mutation within the dra region encoding for Dr fimbriae prevents the development of the tubulointerstitial nephritis.[58] 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.[59] 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.[60]

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.[57] 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.[57],[61]

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.[62] 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.[63] However, the role of LPS in facilitating renal failure and acute allograft injury with ascending UTIs is not well understood.[64]

Bacteria are lysed by a cascade of complement activation system in the human serum.[65] However, UPEC expresses outer membrane proteins, such as traT and Iss, which facilitates the escape of the complement killing.[63] 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.[66] 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[67] and the degree of serum resistance is proportional to the amount of LPS (O antigen) the strain contains.[68] Serum-resistant strains are usually more nephropathogenic than comparable serum-sensitive strains in a variety of models of UTI[69],[70] even though these resistant strains may not be associated with increased lethality.[69] 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

Click here to view


Bacteria secreted virulence factors

Pathogenic strains of E. coli secrete toxins which are vital virulence factors by causing an inflammatory response.


  Toxins Production Top


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.[71] 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.[72]

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.[63],[71],[73],[74] 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.[75],[76],[77],[78],[79] 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.[80]

Hemolytic uropathogenic strains most times also expressPfimbriae.[81] Hemolysin production is usually associated with UPEC strains from patients with pyelonephritis (49%), followed by cystitis isolates and asymptomatic bacteriuria.[82] 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.[83]

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.[84],[85] 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.[86] CNF1 produce by UPEC infringes on polymorphonuclear phagocytosis to elicit apoptosis and scarring of the epithelia of the bladder.[87] In a study of Yamamoto et al.,[88] 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.[89] 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.[90] 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.,[91] 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.[92] Furthermore, there is an often relationship between Usp and all common serotypes of UPEC.[93]

Outer membrane protease T (OmpT) of E. coli is a surface membrane serine protease that catalyzes the activation of plasminogen to plasmin.[94] 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.[95],[96]

UPEC also secrets serine-autotransporter toxin (sat) to intoxicate cell lines of bladder or kidney origin, hence, playing vital activity in UTI pathogenesis.[97],[98] Cytolethal distending toxin (CDT) is another virulence factor in UPEC associated UTIs.[99],[100] 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.[80]


  Iron Upregulation Top


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+).[101],[102] 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.[103]

E. coli has gene present in PAIs which encodes proteins for biosynthesis of the yersiniabactin siderophore and its uptake system.[104] 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.[105] Hancock and Klemm[106] 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.[107],[108] 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.[109]

Studies have shown a relationship between aerobactin system andPfimbriae UPEC isolates from patients with UTI and urosepsis.[110],[111] 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.[62],[112]

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.[113] [Figure 1] shows the diagram of uropathogenic Escherichia coli-associated fitness and virulence.[114]
Figure 1: Uropathogenic Escherichia coli-associated fitness and virulence determinants

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  Phylogenetic Evolution of Uropathogenic Escherichia Coli Top


The strains of the disease-causing and the nondisease E. coli are classified into four main phylogroups groups: A, B1, B2, and D.[115] The basis of this classification into phylogroups is based on inferred evolutionary history through the use of whole-genome sequences to support the phylogenies.[116],[117],[118] 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.[119] 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.[120],[121]

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).[122],[123],[124] 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.[125]


  Molecular Analysis Used in Assaying Uropathogenic Escherichia Coli Pathogenesis Top


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.

Transcriptional profiling

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.[126] This method measures genes which are expressed in a cell at any point in time.[127]

Transposon mutagenesis

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.[128] 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.[129]

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.[129]

DNA microarrays

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.[20],[80],[130],[131]

RNA-seq

This involves the use of high-throughput sequencing platforms such as Illumina in massively parallel sequencing of cDNA libraries utilizing.[131] 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.[132]

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.[133],[134],[135]

Next-generation sequencing

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.[136]

Messerer et al.[137] 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.[138]

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.[139],[140],[141],[142]

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.[143]


  Concluding Remarks Top


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.

Acknowledgments

Special thanks to Mr. Solomon Ben for his contributions to this review.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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