Genomic diversity of EPEC associated with clinical presentations of differing severity

Hazen, Tracy H.; Donnenberg, Michael S.; Panchalingam, Sandra; Antonio, Martín; Hossain, Ahmed; Mandomando, Inácio; Ochieng, John B.; Ramamurthy, Thandavarayan; Tamboura, Boubou; Qureshi, Shahida; Quadri, Farheen; Zaidi, Anita K. M.; Kotloff, Karen L.; Levine, Myron M.; Barry, Eileen M.; Kaper, James B.; Rasko, David A.; Nataro, James P.

doi:10.1038/nmicrobiol.2015.14

Cited by 72 publications

(109 citation statements)

References 43 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Like the evolution of Shigella, that of EIEC was likely driven by the acquisition of the invasion plasmid, as well as some, but not all, of the genes of the Shigella pathogenicity islands. As previously demonstrated for EPEC (29,80), ETEC (30,81), and Shigella (41,82), the same pathovar can occur in evolutionarily diverse lineages. Similar to what we have previously described for the attaching and effacing E. coli pathovars (EPEC and EHEC) (29), Shigella and EIEC include diverse members that have in common virulence mechanisms driven by the acquisition of mobile genetic elementencoded virulence genes (genomic islands, plasmids, or phage).…”

Section: Discussionsupporting

confidence: 65%

Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics

et al. 2016

Self Cite

View full text Add to dashboard Cite

Enteroinvasive Escherichia coli (EIEC) is a unique pathovar that has a pathogenic mechanism nearly indistinguishable from that of Shigella species. In contrast to isolates of the four Shigella species, which are widespread and can be frequent causes of human illness, EIEC causes far fewer reported illnesses each year. In this study, we analyzed the genome sequences of 20 EIEC isolates, including 14 first described in this study. Phylogenomic analysis of the EIEC genomes demonstrated that 17 of the isolates are present in three distinct lineages that contained only EIEC genomes, compared to reference genomes from each of the E. coli pathovars and Shigella species. Comparative genomic analysis identified genes that were unique to each of the three identified EIEC lineages. While many of the EIEC lineage-specific genes have unknown functions, those with predicted functions included a colicin and putative proteins involved in transcriptional regulation or carbohydrate metabolism. In silico detection of the Shigella virulence plasmid (pINV), which is essential for the invasion of host cells, demonstrated that a form of pINV was present in nearly all EIEC genomes, but the Mxi-Spa-Ipa region of the plasmid that encodes the invasion-associated proteins was absent from several of the EIEC isolates. The comparative genomic findings in this study support the hypothesis that multiple EIEC lineages have evolved independently from multiple distinct lineages of E. coli via the acquisition of the Shigella virulence plasmid and, in some cases, the Shigella pathogenicity islands. Enteroinvasive Escherichia coli is a unique group of diseasecausing E. coli bacteria that have a virulence mechanism most similar to that of Shigella bacteria, involving the invasion of intestinal epithelial cells (1-4). In contrast, the other pathovars of E. coli do not invade host cells and, instead, typically associate with the surface of the host cell and secrete or translocate virulence factors onto or into the cell (1, 2, 4). While Shigella bacteria are among the leading agents of diarrheal illness, causing an estimated 165 million annual cases worldwide (5), EIEC bacteria are seldom identified but can occasionally be linked to small food-or waterborne outbreaks (2, 6). Although EIEC bacteria cause disease very similar to the disease caused by Shigella bacteria, they share biochemical and cultural traits that are intermediate between those of commensal E. coli and Shigella bacteria (7). Thus, it is not clear if the reported low incidence is due to the lack of acceptable and defined biochemical/molecular markers for this group or whether EIEC disease truly has a low incidence rate.The virulence of Shigella and EIEC bacteria has been attributed to genes associated with mobile genetic elements including pathogenicity islands and a virulence plasmid, pINV (1-3, 8-11). The pINV plasmid is required for invasion of intestinal epithelial cells and encodes a type III secretion system (T3SS) and many associated effectors (8-10). Meanwhile, on the chromosome,...

show abstract

Section: Discussionsupporting

confidence: 65%

Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, even with a cut-off of 90% the pan-genome is 46,022 genes in this data set and the core genome 1170 genes. Recently, a core of 1080 gene clusters was reported in a study investigating 70 EPEC isolates using large-scale BLAST score ratio analysis (Hazen et al 2016). This is closer to our number of 885 core genes even though the pan-genome in the analysis by Hazen et al (2016) was only 12,964 gene clusters.…”

Section: Wwwgenomeorgsupporting

confidence: 70%

“…Studies have characterized ST131 in detail and highlighted genetic events leading to the success of this lineage. Two studies investigating the origin of enteropathogenic E. coli (EPEC) and atypical enteropathogenic E. coli (aEPEC) and the association of genetic factors with clinical disease severity illustrated the power of WGS by showing that aEPEC and EPEC emerged several times in different lineages (Hazen et al 2016;Ingle et al 2016), and a further study analyzed a global collection of 362 enterotoxigenic E. coli (ETEC) (von Mentzer et al 2014). Smaller studies of local epidemics have concentrated on other pathotypes and single STs.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

et al. 2017

View full text Add to dashboard Cite

Escherichia coli associated with urinary tract infections and bacteremia has been intensively investigated, including recent work focusing on the virulent, globally disseminated, multidrug-resistant lineage ST131. To contextualize ST131 within the broader E. coli population associated with disease, we used genomics to analyze a systematic 11-yr hospital-based survey of E. coli associated with bacteremia using isolates collected from across England by the British Society for Antimicrobial Chemotherapy and from the Cambridge University Hospitals NHS Foundation Trust. Population dynamics analysis of the most successful lineages identified the emergence of ST131 and ST69 and their establishment as two of the five most common lineages along with ST73, ST95, and ST12. The most frequently identified lineage was ST73. Compared to ST131, ST73 was susceptible to most antibiotics, indicating that multidrug resistance was not the dominant reason for prevalence of E. coli lineages in this population. Temporal phylogenetic analysis of the emergence of ST69 and ST131 identified differences in the dynamics of emergence and showed that expansion of ST131 in this population was not driven by sequential emergence of increasingly resistant subclades. We showed that over time, the E. coli population was only transiently disturbed by the introduction of new lineages before a new equilibrium was rapidly achieved. Together, these findings suggest that the frequency of E. coli lineages in invasive disease is driven by negative frequency-dependent selection occurring outside of the hospital, most probably in the commensal niche, and that drug resistance is not a primary determinant of success in this niche.

show abstract

“…The genes of pB171_90 were predicted and annotated using an in-house annotation pipeline (73). These genes were then detected in a collection of 4,798 E. coli genome assemblies available in GenBank as of November 2016, using large-scale BLAST score ratio (LS-BSR) analysis as previously described (74,75). The pB171_90 protein-coding genes were compared to each genome listed in Table S1 using TBLASTN (76) with composition-based adjustment turned off.…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Large Antibiotic Resistance Plasmid Found in Enteropathogenic Escherichia coli Strain B171 and Its Relatedness to Plasmids of Diverse E. coli and Shigella Strains

Hazen

Michalski

Nagaraj

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Enteropathogenic Escherichia coli (EPEC) is a leading cause of severe infantile diarrhea in developing countries. Previous research has focused on the diversity of the EPEC virulence plasmid, whereas less is known regarding the genetic content and distribution of antibiotic resistance plasmids carried by EPEC. A previous study demonstrated that in addition to the virulence plasmid, reference EPEC strain B171 harbors a second, larger plasmid that confers antibiotic resistance. To further understand the genetic diversity and dissemination of antibiotic resistance plasmids among EPEC strains, we describe the complete sequence of an antibiotic resistance plasmid from EPEC strain B171. The resistance plasmid, pB171_90, has a completed sequence length of 90,229 bp, a GC content of 54.55%, and carries protein-encoding genes involved in conjugative transfer, resistance to tetracycline (tetA), sulfonamides (sulI), and mercury, as well as several virulence-associated genes, including the transcriptional regulator hha and the putative calcium sequestration inhibitor (csi). In silico detection of the pB171_90 genes among 4,798 publicly available E. coli genome assemblies indicates that the unique genes of pB171_90 (csi and traI) are primarily restricted to genomes identified as EPEC or enterotoxigenic E. coli. However, conserved regions of the pB171_90 plasmid containing genes involved in replication, stability, and antibiotic resistance were identified among diverse E. coli pathotypes. Interestingly, pB171_90 also exhibited significant similarity with a sequenced plasmid from Shigella dysenteriae type I. Our findings demonstrate the mosaic nature of EPEC antibiotic resistance plasmids and highlight the need for additional sequence-based characterization of antibiotic resistance plasmids harbored by pathogenic E. coli. KEYWORDS EPEC, Escherichia coli, mosaic, plasmidT here has been an alarming increase in the frequency of antibiotic resistance in bacterial pathogens. Multidrug-resistant Enterobacteriaceae are of particular concern and include some groups of disease-causing Escherichia coli (1-3). E. coli strains have been identified that are resistant to all routinely prescribed antibiotics, including colistin, which is a last resort treatment option for carbapenem-resistant Enterobacteriaceae (4-7). The most widely reported antibiotic-resistant E. coli strains are those belonging to multilocus sequence type (MLST) 131 (ST131), which are usually identified as extraintestinal pathogenic E. coli (ExPEC) and often exhibit resistance to fluoroquinolones, as well as extended-spectrum cephalosporins (1,8). E. coli can also serve as a reservoir of antibiotic resistance genes, including mph(A), which confers resistance to macrolides such as azithromycin (9). E. coli strains from healthy volunteers in different

show abstract

Genomic diversity of EPEC associated with clinical presentations of differing severity

Cited by 72 publications

References 43 publications

Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics

Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

Characterization of a Large Antibiotic Resistance Plasmid Found in Enteropathogenic Escherichia coli Strain B171 and Its Relatedness to Plasmids of Diverse E. coli and Shigella Strains

Contact Info

Product

Resources

About