Special Issue "Pathogenesis of Enterohaemorrhagic Escherichia coli"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (30 September 2018)

Special Issue Editor

Guest Editor
Dr. Stephanie Schüller

Norwich Medical School, University of East Anglia, Norwich, UK
Website | E-Mail
Interests: foodborne bacteria; bacterial pathogenesis; host-pathogen interactions; gut microbiota; advanced cell and tissue-based model systems for intestinal infections

Special Issue Information

Dear Colleagues,

Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen that can cause severe systemic disease, particularly in children and the elderly. EHEC virulence is associated with the production of a type III secretion system, enabling injection of bacterial effector proteins into the host cell. Around 40 effectors have been identified so far, which mediate EHEC adherence to intestinal epithelium and modulate various host cell functions, such as ion transport, epithelial permeability, and inflammation. In addition, Shiga toxins released during EHEC infection penetrate into the bloodstream and cause damage to the kidneys and the central nervous system. At present, there is no specific treatment available and a better understanding of the underlying mechanisms of EHEC pathogenesis is needed. In this special issue, I would like to invite you to submit a review or original research article related to virulence factors and mechanisms contributing to EHEC infections in humans.

This Special Issue will contain the extended and enhanced versions of selected papers presented from the 10th International Symposium on VTEC Conference (6–9 May 2018, Florence, Italy, http://www.vtec2018.org/).

Dr. Stephanie Schüller
Guest Editor

Manuscript Submission Information

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Keywords

  • EHEC
  • pathogenesis
  • virulence factors
  • bacteria - host cell interactions
  • adherence
  • host response

Published Papers (9 papers)

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Research

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Open AccessArticle Novel Effector Protein EspY3 of Type III Secretion System from Enterohemorrhagic Escherichia coli Is Localized in Actin Pedestals
Microorganisms 2018, 6(4), 112; https://doi.org/10.3390/microorganisms6040112
Received: 18 September 2018 / Revised: 20 October 2018 / Accepted: 24 October 2018 / Published: 27 October 2018
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Abstract
Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic Escherichia coli (EPEC) are attaching and effacing (A/E) pathogens, which translocate effector proteins to intestinal enterocytes through a type III secretion system (T3SS). T3SS and most of its effector proteins are encoded in a pathogenicity island called [...] Read more.
Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic Escherichia coli (EPEC) are attaching and effacing (A/E) pathogens, which translocate effector proteins to intestinal enterocytes through a type III secretion system (T3SS). T3SS and most of its effector proteins are encoded in a pathogenicity island called LEE. Recently, new effectors have been located outside the LEE. This study aimed to characterize EspY3, a novel non-LEE encoded T3SS effector of EHEC. EspY3 shares homology with SopD and PipB2 effector proteins of Salmonella’s T3SS-1 and T3SS-2, respectively. The presence of recombinant EspY3 in the supernatant samples demonstrated that EspY3 was secreted by the T3SS of EHEC and EPEC. Through infection assays, we demonstrated the translocation of EspY3 into Caco-2 cells by T3SS of EPEC. The subcellular localization of EspY3 was determined in the pedestal region, where its presence generates a significant increase in the size of the pedestals area. The EspY3 effector induced the elongation of polymerized actin pedestals in infected Caco-2 by EPEC. This study confirmed that EspY3 is part of the repertoire of T3SS effectors of EHEC O157:H7, and that it participates in modeling cellular actin during the infection. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Open AccessArticle Variability in Characterizing Escherichia coli from Cattle Feces: A Cautionary Tale
Microorganisms 2018, 6(3), 74; https://doi.org/10.3390/microorganisms6030074
Received: 15 June 2018 / Revised: 17 July 2018 / Accepted: 20 July 2018 / Published: 21 July 2018
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Abstract
Shiga toxin-producing Escherichia coli (STEC) are diverse bacteria, with seven serogroups (O26, O45, O103, O111, O121, O145, O157; “Top 7”) of interest due to their predominance in human disease. Confirmation of STEC relies on a combination of culturing, immunological and molecular assays, but [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) are diverse bacteria, with seven serogroups (O26, O45, O103, O111, O121, O145, O157; “Top 7”) of interest due to their predominance in human disease. Confirmation of STEC relies on a combination of culturing, immunological and molecular assays, but no single gold standard for identification exists. In this study, we compared analysis of STEC between three independent laboratories (LAB) using different methodologies. In LAB A, colonies of Top 7 were picked after serogroup-specific immunomagnetic separation of feces from western-Canadian slaughter cattle. A fraction of each colony was tested by PCR (stx1, stx2, eae, O group), and Top 7 isolates were saved as glycerol stocks (n = 689). In LAB B, a subsample of isolates (n = 171) were evaluated for stx1 and stx2 using different primer sets. For this, approximately half of the PCR were performed using original DNA template provided by LAB A and half using DNA extracted from sub-cultured isolates. All Top 7 isolates were sub-cultured by LAB A and shipped to LAB C for traditional serotyping (TS) to determine O and H groups, with PCR-confirmation of virulence genes using a third set of primers. By TS, 76% of O groups (525/689) matched PCR-determined O groups. Lowest proportions (p < 0.05) of O group matches between PCR and TS (62.6% and 69.8%) occurred for O26 and O45 serogroups, respectively. PCR-detection of stx differed most between LAB A and LAB C. Excluding isolates where O groups by PCR and TS did not match, detection of stx1 was most consistent (p < 0.01) for O111 and O157:H7/NM. In contrast, for O45 and O103, stx1 was detected in >65% of isolates by LAB A and <5% by LAB C. Stx2 was only detected by LAB C in isolates of serogroups O121, O145, and O157:H7/NM. LAB B also detected stx2 in O26 and O157:H12/H29, while LAB A detected stx2 in all serogroups. Excluding O111 and O157:H7/NM, marked changes in stx detection were observed between initial isolation and sub-cultures of the same isolate. While multiple explanations exist for discordant O-typing between PCR and TS and for differences in stx detection across labs, these data suggest that assays for STEC classification may require re-evaluation and/or standardization. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Open AccessArticle Zoonotic Fecal Pathogens and Antimicrobial Resistance in Canadian Petting Zoos
Microorganisms 2018, 6(3), 70; https://doi.org/10.3390/microorganisms6030070
Received: 12 June 2018 / Revised: 9 July 2018 / Accepted: 11 July 2018 / Published: 16 July 2018
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Abstract
This study aimed to better understand the potential public health risk associated with zoonotic pathogens in agricultural fairs and petting zoos in Canada. Prevalence of Salmonella, Shiga toxin-producing Escherichia coli (STEC) O157:H7, and top six non-O157 STEC serogroups in feces (n [...] Read more.
This study aimed to better understand the potential public health risk associated with zoonotic pathogens in agricultural fairs and petting zoos in Canada. Prevalence of Salmonella, Shiga toxin-producing Escherichia coli (STEC) O157:H7, and top six non-O157 STEC serogroups in feces (n = 88), hide/feather (n = 36), and hand rail samples (n = 46) was assessed, as well as distributions of antimicrobial resistant (AMR) broad and extended-spectrum β-lactamase (ESBL)-producing E. coli. Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in pig nasal swabs (n = 4), and Campylobacter, Cryptosporidium, and Giardia in feces was also assessed. Neither Salmonella nor MRSA were detected. Campylobacter spp. were isolated from 32% of fecal samples. Cryptosporidium and Giardia were detected in 2% and 15% of fecal samples, respectively. Only one fecal sample was positive for STEC O157, whereas 22% were positive for non-O157 STEC. Multi-drug resistance (MDR) to antibiotics classified as critically and highly important in human medicine was proportionally greatest in E. coli from cattle feces. The β-lactamase-producing E. coli from pig, horse/donkey feces, and hand rail samples, as well as the STEC E. coli from handrail swabs were MDR. The diversity and prevalence of zoonotic pathogens and AMR bacteria detected within agricultural fairs and petting zoos emphasize the importance of hygienic practices and sanitization with respect to reducing associated zoonotic risks. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Review

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Open AccessReview Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome
Microorganisms 2019, 7(1), 15; https://doi.org/10.3390/microorganisms7010015
Received: 19 November 2018 / Revised: 21 December 2018 / Accepted: 7 January 2019 / Published: 10 January 2019
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Abstract
Shiga toxin (Stx)-producing Escherichia coli (STEC) infections have become a threat to public health globally because of the severe illnesses that they can trigger, such as hemorrhagic colitis and the post-diarrheal hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute [...] Read more.
Shiga toxin (Stx)-producing Escherichia coli (STEC) infections have become a threat to public health globally because of the severe illnesses that they can trigger, such as hemorrhagic colitis and the post-diarrheal hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. Glomerular endothelial cells are primary targets of Stx which, after binding to its specific receptor globotriaosylceramide, upregulates proinflammatory proteins involved both in the recruitment and adhesion of leukocytes and thrombus formation at the site of endothelial injury. In this review, we discuss the role of complement activation in promoting glomerular microvascular dysfunction, providing evidence from experimental models and patients with STEC-HUS. Within the glomerulus, an important target for Stx-induced complement activation is the podocyte, a cell type that is in close contact with endothelial cells and participates in maintaining the filtration barrier. Recently, podocyte injury and loss have been indicated as potential risk factors for long-term renal sequelae in patients with STEC-HUS. Therapeutic approaches targeting the complement system, that may be useful options for patients with STEC-HUS, will also be discussed. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Open AccessReview Modulation of Enterohaemorrhagic Escherichia coli Survival and Virulence in the Human Gastrointestinal Tract
Microorganisms 2018, 6(4), 115; https://doi.org/10.3390/microorganisms6040115
Received: 3 October 2018 / Revised: 16 November 2018 / Accepted: 18 November 2018 / Published: 19 November 2018
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Abstract
Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain [...] Read more.
Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain poorly described, due to a paucity of relevant model systems. This review will provide an overview of the in vitro and in vivo studies investigating the effect of abiotic (e.g., gastric acid, bile, low oxygen concentration or fluid shear) and biotic (e.g., gut microbiota, short chain fatty acids or host hormones) parameters of the human gut on EHEC survival and/or virulence (especially in relation with motility, adhesion and toxin production). Despite their relevance, these studies display important limitations considering the complexity of the human digestive environment. These include the evaluation of only one single digestive parameter at a time, lack of dynamic flux and compartmentalization, and the absence of a complex human gut microbiota. In a last part of the review, we will discuss how dynamic multi-compartmental in vitro models of the human gut represent a novel platform for elucidating spatial and temporal modulation of EHEC survival and virulence along the GIT, and provide new insights into EHEC pathogenesis. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Open AccessReview Shiga Toxin-Producing Escherichia coli Infections during Pregnancy
Microorganisms 2018, 6(4), 111; https://doi.org/10.3390/microorganisms6040111
Received: 26 September 2018 / Revised: 17 October 2018 / Accepted: 19 October 2018 / Published: 23 October 2018
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Abstract
Gastrointestinal infection with Shiga toxin-producing Escherichia coli (STEC) causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS), characterized by hemolytic anemia, thrombocytopenia and acute renal failure. The main virulence factor of STEC is Shiga toxin (Stx), which is responsible for HUS development. STEC [...] Read more.
Gastrointestinal infection with Shiga toxin-producing Escherichia coli (STEC) causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS), characterized by hemolytic anemia, thrombocytopenia and acute renal failure. The main virulence factor of STEC is Shiga toxin (Stx), which is responsible for HUS development. STEC can produce Stx type 1 and/or 2 (Stx1, Stx2) and their variants, Stx2 being more frequently associated with severe cases of HUS. This pathology occurs in 5–15% of cases with STEC infection when Stx gain access to the bloodstream and causes damage in the target organs such as the kidney and brain. STEC infections affect mainly young children, although the large HUS outbreak with a new Stx2-producing STEC O104:H4 in Europe in 2011 involved more adults than children, and women were over-represented. Maternal infections during pregnancy are associated with adverse pregnancy outcomes. Studies in rats showed that Stx2 binds to the utero-placental unit and causes adverse pregnancy outcomes. In this article, we provide a brief overview of Stx2 action on placental tissues and discuss whether they might cause pregnancy loss or preterm birth. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Open AccessReview Recent Advances in Shiga Toxin-Producing Escherichia coli Research in Latin America
Microorganisms 2018, 6(4), 100; https://doi.org/10.3390/microorganisms6040100
Received: 6 August 2018 / Revised: 1 September 2018 / Accepted: 28 September 2018 / Published: 28 September 2018
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Abstract
Pathogenic Escherichia coli are known to be a common cause of diarrheal disease and a frequently occurring bacterial infection in children and adults in Latin America. Despite the effort to combat diarrheal infections, the south of the American continent remains a hot spot [...] Read more.
Pathogenic Escherichia coli are known to be a common cause of diarrheal disease and a frequently occurring bacterial infection in children and adults in Latin America. Despite the effort to combat diarrheal infections, the south of the American continent remains a hot spot for infections and sequelae associated with the acquisition of one category of pathogenic E. coli, the Shiga toxin-producing E. coli (STEC). This review will focus on an overview of the prevalence of different STEC serotypes in human, animals and food products, focusing on recent reports from Latin America outlining the recent research progress achieved in this region to combat disease and endemicity in affected countries and to improve understanding on emerging serotypes and their virulence factors. Furthermore, this review will highlight the progress done in vaccine development and treatment and will also discuss the effort of the Latin American investigators to respond to the thread of STEC infections by establishing a multidisciplinary network of experts that are addressing STEC-associated animal, human and environmental health issues, while trying to reduce human disease. Regardless of the significant scientific contributions to understand and combat STEC infections worldwide, many significant challenges still exist and this review has focus in the Latin American efforts as an example of what can be accomplished when multiple groups have a common goal. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Open AccessReview Genotypic Features of Clinical and Bovine Escherichia coli O157 Strains Isolated in Countries with Different Associated-Disease Incidences
Microorganisms 2018, 6(2), 36; https://doi.org/10.3390/microorganisms6020036
Received: 28 March 2018 / Revised: 20 April 2018 / Accepted: 25 April 2018 / Published: 27 April 2018
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Abstract
There is great geographical variation in the frequency of Escherichia coli O157 infections that correlates with important differences in the bovine reservoir of each country. Our group carried out a broad molecular characterization of human and bovine E. coli O157 strains circulating in [...] Read more.
There is great geographical variation in the frequency of Escherichia coli O157 infections that correlates with important differences in the bovine reservoir of each country. Our group carried out a broad molecular characterization of human and bovine E. coli O157 strains circulating in Argentina using different methodologies. Our data allows us to conclude that in Argentina, a high homogeneity is observed in both cattle and human strains, with almost exclusive circulation of strains belonging to the hypervirulent clade 8 described by Manning. The aim of this review was to compare the genetic background of E. coli O157 strains isolated in countries that have conducted similar studies, to try to correlate specific O157 genotypes with the incidence and severity of E. coli O157 associated diseases. The characteristics of the strains that cause disease in humans reflect the predominant genotypes in cattle in each of the countries analyzed. The main features clearly linked to high incidence or severity of E. coli O157 infections are lineage-specific polymorphism assay-6 lineage I/II, clade 8 strains and probably, clade 6 strains, the stx2a/stx2c genotype, the presence of q933 and q21 simultaneously, and putative virulence factor EC_3286. In countries with an absence of these features in O157 strains, the overall incidence of O157 disease is low. Argentina, where these characteristics are detected in most strains, shows the highest incidence of hemolytic uremic syndrome (HUS) worldwide. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)

Other

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Open AccessBrief Report Antimicrobial Resistance in Class 1 Integron-Positive Shiga Toxin-Producing Escherichia coli Isolated from Cattle, Pigs, Food and Farm Environment
Microorganisms 2018, 6(4), 99; https://doi.org/10.3390/microorganisms6040099
Received: 18 August 2018 / Revised: 24 September 2018 / Accepted: 26 September 2018 / Published: 28 September 2018
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Abstract
The aim of this study was to investigate the presence of class 1 integrons in a collection of Shiga toxin-producing Escherichia coli (STEC) from different origins and to characterize pheno- and genotypically the antimicrobial resistance associated to them. A collection of 649 isolates [...] Read more.
The aim of this study was to investigate the presence of class 1 integrons in a collection of Shiga toxin-producing Escherichia coli (STEC) from different origins and to characterize pheno- and genotypically the antimicrobial resistance associated to them. A collection of 649 isolates were screened for the class 1 integrase gene (intI1) by Polymerase chain reaction The variable region of class 1 integrons was amplified and sequenced. Positive strains were evaluated for the presence of antimicrobial resistance genes with microarray and for antimicrobial susceptibility by the disk diffusion method. Seven out of 649 STEC strains some to serogroups, O26, O103 and O130 isolated from cattle, chicken burger, farm environment and pigs were identified as positive for intl1. Different arrangements of gene cassettes were detected in the variable region of class 1 integron: dfrA16, aadA23 and dfrA1-aadA1. In almost all strains, phenotypic resistance to streptomycin, tetracycline, trimethoprim/sulfamethoxazole, and sulfisoxazole was observed. Microarray analyses showed that most of the isolates carried four or more antimicrobial resistance markers and STEC strains were categorized as Multridrug-resistant. Although antimicrobials are not usually used in the treatment of STEC infections, the presence of Multridrug-resistant in isolates collected from farm and food represents a risk for animal and human health. Full article
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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