Whole-Genome Characterization and Strain Comparison of VT2f-Producing<i>Escherichia</i><i>coli</i>Causing Hemolytic Uremic Syndrome

Grande, Laura; Michelacci, Valeria; Bondì, Roslen; Gigliucci, Federica; Franz, Eelco; Badouei, Mahdi Askari; Schlager, Sabine; Minelli, Fabio; Tozzoli, Rosangela; Caprioli, Alfredo; Morabito, Stefano

doi:10.3201/eid2212.160017

Cited by 29 publications

(25 citation statements)

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“…Accordingly, the phylogenetic and structural analyses showed the phage phi467, carrying the Stx2f-coding genes, falling into a clade separated from the others ( Figures 3 – 5 ). We did not include many Stx2f-encoding phages in this study as they are not available in the public databases for downloading, but previous evidences showed that these phages share a very high degree of similarity ( Grande et al, 2016 ). It is thus conceivable that they could have descended from a common ancestor and possibly remained confined to the pigeon host.…”

Section: Discussionmentioning

confidence: 99%

Investigation on the Evolution of Shiga Toxin-Converting Phages Based on Whole Genome Sequencing

et al. 2020

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Bacteriophages are pivotal elements in the dissemination of virulence genes. The main virulence determinants of Shiga Toxin producing E. coli, Shiga Toxins (Stx), are encoded by genes localized in the genome of lambdoid bacteriophages. Stx comprise two antigenically different types, Stx1 and Stx2, further divided into subtypes. Among these, certain Stx2 subtypes appear to be more commonly occurring in the most severe forms of the STEC disease, haemorrhagic colitis and haemolytic uremic syndrome (HUS). This study aimed at obtaining insights on the evolution of Stx2 bacteriophages, due to their relevance in public health, and we report here on the analysis of the genomic structure of Stx2 converting phages in relation with the known reservoir of the E. coli strains harboring them. Stx2-converting phages conveying the genes encoding different stx2 subtypes have been isolated from STEC strains and their whole genomes have been sequenced, analyzed and compared to those of other Stx2 phages available in the public domain. The phages' regions containing the stx2 genes have been analyzed in depth allowing to make inference on the possible mechanisms of selection and maintenance of certain Stx2 phages in the reservoir. The "stx regions" of different stx2 gene subtypes grouped into three different evolutionary lines in the comparative analysis, reflecting the frequency with which these subtypes are found in different animal niches, suggesting that the colonization of specific reservoir by STEC strains could be influenced by the Stx phage that they carry. Noteworthy, we could identify the presence of nanS-p gene exclusively in the "stx regions" of the phages identified in STEC strains commonly found in cattle. As a matter of fact, this gene encodes an esterase capable of metabolizing sialic acids produced by submaxillary glands of bovines and present in great quantities in their gastrointestinal tract.

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Section: Discussionmentioning

confidence: 99%

Investigation on the Evolution of Shiga Toxin-Converting Phages Based on Whole Genome Sequencing

et al. 2020

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“…Subtypes Stx2a, Stx2c and Stx2d are associated with STEC infections in humans [11,15,16,17], while Stx2e, Stx2f, Stx2g are mainly found in animals [2,10,11]. Some studies have suggested that STEC strains producing Stx2f can cause diarrhoea in humans [18]; however, recently, STEC strains carrying the stx2f gene have been isolated from patients with hemolytic uremic syndrome (HUS) [18,19].…”

Section: Introductionmentioning

confidence: 99%

Presence of Shiga Toxin-Producing Escherichia coli (STEC) in Fresh Beef Marketed in 13 Regions of ITALY (2017)

et al. 2018

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The aim of this study was to determine the prevalence of Shiga toxin-producing Escherichia coli in fresh beef marketed in 2017 in 13 regions of Italy, to evaluate the potential risk to human health. According to the ISO/TS 13136:2012 standard, 239 samples were analysed and nine were STEC positive, from which 20 strains were isolated. The STEC-positive samples were obtained from Calabria (n = 1), Campania (n = 1), Lazio (n = 2), Liguria (n = 1), Lombardia (n = 1) and Veneto (n = 3). All STEC strains were analysed for serogroups O26, O45, O55, O91, O103, O104, O111, O113, O121, O128, O145, O146 and O157, using Real-Time PCR. Three serogroups were identified amongst the 20 strains: O91 (n = 5), O113 (n = 2), and O157 (n = 1); the O-group for each of the 12 remaining STEC strains was not identified. Six stx subtypes were detected: stx1a, stx1c, stx2a, stx2b, stx2c and stx2d. Subtype stx2c was the most common, followed by stx2d and stx2b. Subtype stx2a was identified in only one eae-negative strain and occurred in combination with stx1a, stx1c and stx2b. The presence in meat of STEC strains being potentially harmful to human health shows the importance, during harvest, of implementing additional measures to reduce contamination risk.

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“…Striking phage-related variability in toxin production has been observed in clinical isolates of O157 as well as in other O groups (O83, O111, and O145). The genotype of the bacteriophage and host strain factors are relevant to STEC pathogenesis (158) as was recently demonstrated in a whole genome sequencing comparison of Stx2f-producing STEC strains, some of which were isolated from patients with HUS (63). In that study, only the three strains isolated from HUS patients had the EPECassociated efa1 gene, which resides on the PAI OI122, the STEC plasmid genes ehxA, espP, and katP, and intimin type n (xi) or b.…”

Section: Stx Types and Subtypesmentioning

confidence: 80%

“…Some studies suggested that an STEC strain that produce Stx2f can cause mild diarrhea or can be asymptomatic (54,126), but it appears to be rare (71,124). However, in a recent study an STEC O8:H19 strain that carried both stx 2f and eae was isolated from an HUS patient in The Netherlands (53), and others have also reported isolating Stx2f-producing STEC strains from HUS patients (63). Additional information is needed to understand the association between Stx2f and severe illness.…”

Section: Stx Types and Subtypesmentioning

confidence: 99%

Hazard Identification and Characterization: Criteria for Categorizing Shiga Toxin–Producing Escherichia coli on a Risk Basis†

Expert¹

2019

Journal of Food Protection

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Shiga toxin–producing Escherichia coli (STEC) comprise a large, highly diverse group of strains. Since the emergence of STEC serotype O157:H7 as an important foodborne pathogen, serotype data have been used for identifying STEC strains, and this use continued as other serotypes were implicated in human infections. An estimated 470 STEC serotypes have been identified, which can produce one or more of the 12 known Shiga toxin (Stx) subtypes. The number of STEC serotypes that cause human illness varies but is probably higher than 100. However, many STEC virulence genes are mobile and can be lost or transferred to other bacteria; therefore, STEC strains that have the same serotype may not carry the same virulence genes or pose the same risk. Although serotype information is useful in outbreak investigations and surveillance studies, it is not a reliable means of assessing the human health risk posed by a particular STEC serotype. To contribute to the development of a set of criteria that would more reliably support hazard identification, this review considered each of the factors contributing to a negative human health outcome: mild diarrhea, bloody diarrhea, and hemolytic uremic syndrome (HUS). STEC pathogenesis involves entry into the human gut (often via ingestion), attachment to the intestinal epithelial cells, and elaboration of Stx. Production of Stx, which disrupts normal cellular functions and causes cell damage, alone without adherence of bacterial cells to gut epithelial cells is insufficient to cause severe illness. The principal adherence factor in STEC is the intimin protein coded by the eae gene. The aggregative adherence fimbriae adhesins regulated by the aggR gene of enteroaggregative E. coli strains are also effective adherence factors. The stx2a gene is most often present in locus of enterocyte effacement (eae)–positive STEC strains and has consistently been associated with HUS. The stx2a gene has also been found in eae-negative, aggR-positive STEC that have caused HUS. HUS cases where other stx gene subtypes were identified indicate that other factors such as host susceptibility and the genetic cocktail of virulence genes in individual isolates may affect their association with severe diseases.

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Whole-Genome Characterization and Strain Comparison of VT2f-ProducingEscherichiacoliCausing Hemolytic Uremic Syndrome

Abstract: Strains from diarrheal illnesses could be transmitted from pigeons, but HUS-associated strains may derive from phage acquisition by isolates with larger virulence assets.

Cited by 29 publications

References 39 publications

Investigation on the Evolution of Shiga Toxin-Converting Phages Based on Whole Genome Sequencing

Investigation on the Evolution of Shiga Toxin-Converting Phages Based on Whole Genome Sequencing

Presence of Shiga Toxin-Producing Escherichia coli (STEC) in Fresh Beef Marketed in 13 Regions of ITALY (2017)

Hazard Identification and Characterization: Criteria for Categorizing Shiga Toxin–Producing Escherichia coli on a Risk Basis†

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