Model-based clustering of Escherichia coli O157:H7 genotypes and their potential association with clinical outcome in human infections

Elhadidy, Mohamed; Elkhatib, Walid F.; Piérard, Denis; Reu, Koen De; Heyndrickx, Marc

doi:10.1016/j.diagmicrobio.2015.06.016

Cited by 3 publications

(6 citation statements)

References 34 publications

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“…Expanding these sequence-based analyses to the publicly available EHEC sequence pool will improve public health response in the event of an outbreak allowing timely and informed countermeasures. Canonical SNPs can be implemented in efficient typing assays offering robust phylogenetic signals for outbreak exclusion/inclusion that surpass classical technologies (Riordan et al, 2008 ; Elhadidy et al, 2015 ; Rusconi and Eppinger, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Whole Genome Sequencing for Genomics-Guided Investigations of Escherichia coli O157:H7 Outbreaks

et al. 2016

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Multi isolate whole genome sequencing (WGS) and typing for outbreak investigations has become a reality in the post-genomics era. We applied this technology to strains from Escherichia coli O157:H7 outbreaks. These include isolates from seven North America outbreaks, as well as multiple isolates from the same patient and from different infected individuals in the same household. Customized high-resolution bioinformatics sequence typing strategies were developed to assess the core genome and mobilome plasticity. Sequence typing was performed using an in-house single nucleotide polymorphism (SNP) discovery and validation pipeline. Discriminatory power becomes of particular importance for the investigation of isolates from outbreaks in which macrogenomic techniques such as pulse-field gel electrophoresis or multiple locus variable number tandem repeat analysis do not differentiate closely related organisms. We also characterized differences in the phage inventory, allowing us to identify plasticity among outbreak strains that is not detectable at the core genome level. Our comprehensive analysis of the mobilome identified multiple plasmids that have not previously been associated with this lineage. Applied phylogenomics approaches provide strong molecular evidence for exceptionally little heterogeneity of strains within outbreaks and demonstrate the value of intra-cluster comparisons, rather than basing the analysis on archetypal reference strains. Next generation sequencing and whole genome typing strategies provide the technological foundation for genomic epidemiology outbreak investigation utilizing its significantly higher sample throughput, cost efficiency, and phylogenetic relatedness accuracy. These phylogenomics approaches have major public health relevance in translating information from the sequence-based survey to support timely and informed countermeasures. Polymorphisms identified in this work offer robust phylogenetic signals that index both short- and long-term evolution and can complement currently employed typing schemes for outbreak ex- and inclusion, diagnostics, surveillance, and forensic studies.

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Section: Discussionmentioning

confidence: 99%

Whole Genome Sequencing for Genomics-Guided Investigations of Escherichia coli O157:H7 Outbreaks

et al. 2016

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“…When stress resistance parameters ( D -values) were compared among STEC O157:H7 genotypes, significant differences were observed for acid, heat, oxidative, cold, and starvation stresses. Interestingly, lineage I/II, tir ( 255T ), and clade 8 encoding strains, which showed a significantly higher resistance to acid, cold, and starvation stresses, have been shown in different studies to be more virulent and more frequently associated with human infection than their counterparts ( Bono et al, 2007 ; Manning et al, 2008 ; Elhadidy et al, 2015b ). On the contrary, some of these genotypes more commonly associated with human disease were significantly less resistant to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Also, some investigators have previously suggested that tir ( 255T ) harboring strains are more virulent for humans than tir ( 255A ) harboring strains ( Bono et al, 2007 ; Franz et al, 2012 ; Mellor et al, 2013 ). In fact, the tir ( 255T ) genotype has been suggested to be the most distinctive genotype for the detection of bacterial clones with potential risk for human illness from food sources ( Elhadidy et al, 2015a ) and has been proposed as an attractive candidate to be used as a surrogate marker for tracking highly severe STEC infections ( Elhadidy et al, 2015b ). Overall, these results suggest that the increased prevalence of E. coli O157:H7 illness observed among lineage I/II, tir ( 255T ), and clade 8 genotypes might be related to the greater stress robustness of these genotypes, a characteristic that likely facilitates transmission of E. coli O157:H7 throughout the food chain and influences the disease causing potential of the pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…This was originally attributed to the possibility that only a subset of genotypes was involved in human infection and this subset would represent a minor subpopulation of the strains of bovine origin ( Franz et al, 2012 ). This divergence is suggested to be crucial and advices a close tracking of clinical-biased strains that are more closely associated with human disease, likely have a high risk for virulence and transmission potential to humans ( Franz et al, 2012 ; Mellor et al, 2013 ; Elhadidy et al, 2015a ) and/or are more correlated with severe clinical symptoms ( Manning et al, 2008 ; Elhadidy et al, 2015b ). Whether the intermediate habitat (in particular the farm to fork chain) of E. coli O157:H7 plays a significant role in the shaping of clinical populations remains obscure.…”

Section: Introductionmentioning

confidence: 99%

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Diversity of Survival Patterns among Escherichia coli O157:H7 Genotypes Subjected to Food-Related Stress Conditions

Elhadidy

Álvarez‐Ordóñez

2016

Front. Microbiol.

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The purpose of this study was to evaluate the resistance patterns to food-related stresses of Shiga toxin producing Escherichia coli O157:H7 strains belonging to specific genotypes. A total of 33 E. coli O157:H7 strains were exposed to seven different stress conditions acting as potential selective pressures affecting the transmission of E. coli O157:H7 to humans through the food chain. These stress conditions included cold, oxidative, osmotic, acid, heat, freeze-thaw, and starvation stresses. The genotypes used for comparison included lineage-specific polymorphism, Shiga-toxin-encoding bacteriophage insertion sites, clade type, tir (A255T) polymorphism, Shiga toxin 2 subtype, and antiterminator Q gene allele. Bacterial resistance to different stressors was calculated by determining D-values (times required for inactivation of 90% of the bacterial population), which were then subjected to univariate and multivariate analyses. In addition, a relative stress resistance value, integrating resistance values to all tested stressors, was calculated for each bacterial strain and allowed for a ranking-type classification of E. coli O157:H7 strains according to their environmental robustness. Lineage I/II strains were found to be significantly more resistant to acid, cold, and starvation stress than lineage II strains. Similarly, tir (255T) and clade 8 encoding strains were significantly more resistant to acid, heat, cold, and starvation stress than tir (255A) and non-clade 8 strains. Principal component analysis, which allows grouping of strains with similar stress survival characteristics, separated strains of lineage I and I/II from strains of lineage II, which in general showed reduced survival abilities. Results obtained suggest that lineage I/II, tir (255T), and clade 8 strains, which have been previously reported to be more frequently associated with human disease cases, have greater multiple stress resistance than strains of other genotypes. The results from this study provide a better insight into how selective pressures encountered through the food chain may play a role in the epidemiology of STEC O157:H7 through controlling the transmission of highly adapted strains to humans.

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“…Pathogenicity in humans is inexorably linked to the Stx litres produced by individual STEC strains [15, 16]. Hypervirulent clones, as manifested by increased Stx 2a -litres [17–24], have been associated with STEC subpopulations through phylogenetic, epidemiological, and phenotypic linkage [4, 5, 11, 19, 20, 25–49]. The specific factors responsible for elevated Stx-production in hypervirulent STEC strains are unknown but presumably modulated by a number of biotic and abiotic triggers [6, 8, 50–54].…”

Section: Introductionmentioning

confidence: 99%

Pathogenomes and variations in Shiga toxin production among geographically distinct clones of Escherichia coli O113:H21

et al. 2022

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Infections with globally disseminated Shiga toxin-producing Escherichia coli (STEC) of the O113:H21 serotype can progress to severe clinical complications, such as hemolytic uremic syndrome (HUS). Two phylogeographically distinct clonal complexes have been established by multi locus sequence typing (MLST). Infections with ST-820 isolates circulating exclusively in Australia have caused severe human disease, such as HUS. Conversely, ST-223 isolates prevalent in the US and outside Australia seem to rarely cause severe human disease but are frequent contaminants. Following a genomic epidemiology approach, we wanted to gain insights into the underlying cause for this disparity. We examined the plasticity in the genome make-up and Shiga toxin production in a collection of 20 ST-820 and ST-223 strains isolated from produce, the bovine reservoir, and clinical cases. STEC are notorious for assembly into fragmented draft sequences when using short-read sequencing technologies due to the extensive and partly homologous phage complement. The application of long-read technology (LRT) sequencing yielded closed reference chromosomes and plasmids for two representative ST-820 and ST-223 strains. The established high-resolution framework, based on whole genome alignments, single nucleotide polymorphism (SNP)-typing and MLST, includes the chromosomes and plasmids of other publicly available O113:H21 sequences and allowed us to refine the phylogeographical boundaries of ST-820 and ST-223 complex isolates and to further identify a historic non-shigatoxigenic strain from Mexico as a quasi-intermediate. Plasmid comparison revealed strong correlations between the strains’ featured pO113 plasmid genotypes and chromosomally inferred ST, which suggests coevolution of the chromosome and virulence plasmids. Our pathogenicity assessment revealed statistically significant differences in the Stx2a-production capabilities of ST-820 as compared to ST-223 strains under RecA-induced Stx phage mobilization, a condition that mimics Stx-phage induction. These observations suggest that ST-820 strains may confer an increased pathogenic potential in line with the strain-associated epidemiological metadata. Still, some of the tested ST-223 cultures sourced from contaminated produce or the bovine reservoir also produced Stx at levels comparable to those of ST-820 isolates, which calls for awareness and for continued surveillance of this lineage.

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Model-based clustering of Escherichia coli O157:H7 genotypes and their potential association with clinical outcome in human infections

Cited by 3 publications

References 34 publications

Whole Genome Sequencing for Genomics-Guided Investigations of Escherichia coli O157:H7 Outbreaks

Whole Genome Sequencing for Genomics-Guided Investigations of Escherichia coli O157:H7 Outbreaks

Diversity of Survival Patterns among Escherichia coli O157:H7 Genotypes Subjected to Food-Related Stress Conditions

Pathogenomes and variations in Shiga toxin production among geographically distinct clones of Escherichia coli O113:H21

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