Submit to Toxins Review for Toxins Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 53532

Share This Special Issue

Special Issue Editor

Dr. Kim Stanford

E-Mail Website
Guest Editor

Department of Biological Sciences, University of Lethbridge, 4401 University Dr., Lethbridge, AB T1K 3M4, Canada
Interests: food and feed-borne pathogens; Escherichia coli; ergot alkaloids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Shiga toxin-producing Escherichia coli (STEC) are food-borne pathogens implicated in sporadic as well as national and international outbreaks of disease. Cattle and other ruminants are identified reservoirs of these organisms, which are erratically shed in feces. Although cattle are colonized with a diverse population of STEC, a relatively small proportion has been linked to human disease. A central question is how best to conclusively identify Escherichia coli that will lead to human disease. The abundance and persistence of Escherichia coli strains in animal hosts and the environment have been proposed as factors affecting the likelihood of strain pathogenicity, but what factors contribute to strain abundance and persistence? What virulence or other factors determine the pathogenicity of Escherichia coli? In addition, the genetic plasticity of Escherichia coli leading to the loss or gain of Shiga toxins and other virulence factors increases the difficulty of identifying potential pathogens, especially among non-O157 E. coli.

The focus of this Special Issue of Toxins will be on the pathogenicity of enterohemorrhagic Escherichia coli including: factors increasing the survival, abundance or persistence in the environment or animal hosts; the molecular basis of infections; molecular or other assays for the detection of E. coli causing disease; possible interventions to decrease the production of Shiga toxins or other virulence factors and control disease. The ultimate aim would be a reduction in future STEC outbreaks and improved outcomes for STEC patients.

Dr. Kim Stanford
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Enterohemorrhagic Escherichia coli
Shiga toxins
virulence factors
environmental persistence
detection
human infection
interventions

Published Papers (11 papers)

Download All Papers

Editorial

Jump to: Research, Review

2 pages, 196 KiB

Open AccessEditorial

Introduction to the Special Issue “Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections”

by Kim Stanford

Toxins 2020, 12(12), 763; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120763 - 03 Dec 2020

Cited by 1 | Viewed by 1406

Abstract

Although much of the world has progressed since the 1980s, our ability to treat infections with enterohemorrhagic Escherichia coli (EHEC) has unfortunately shown little improvement [...] Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

Research

Jump to: Editorial, Review

16 pages, 2511 KiB

Open AccessArticle

Shiga Toxin Uptake and Sequestration in Extracellular Vesicles Is Mediated by Its B-Subunit

by Annie Willysson, Anne-lie Ståhl, Daniel Gillet, Julien Barbier, Jean-Christophe Cintrat, Valérie Chambon, Anne Billet, Ludger Johannes and Diana Karpman

Toxins 2020, 12(7), 449; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12070449 - 10 Jul 2020

Cited by 12 | Viewed by 3687

Abstract

Shiga toxin (Stx)-stimulated blood cells shed extracellular vesicles (EVs) which can transfer the toxin to the kidneys and lead to hemolytic uremic syndrome. The toxin can be taken up by renal cells within EVs wherein the toxin is released, ultimately leading to cell death. The mechanism by which Stx is taken up, translocated, and sequestered in EVs was addressed in this study utilizing the B-subunit that binds to the globotriaosylceramide (Gb3) receptor. We found that Stx1B was released in EVs within minutes after stimulation of HeLa cells or red blood cells, detected by live cell imaging and flow cytometry. In the presence of Retro-2.1, an inhibitor of intracellular retrograde trafficking, a continuous release of Stx-positive EVs occurred. EVs from HeLa cells possess the Gb3 receptor on their membrane, and EVs from cells that were treated with a glycosylceramide synthase inhibitor, to reduce Gb3, bound significantly less Stx1B. Stx1B was detected both on the membrane and within the shed EVs. Stx1B was incubated with EVs derived from blood cells, in the absence of cells, and was shown to bind to, and be taken up by, these EVs, as demonstrated by electron microscopy. Using a membrane translocation assay we demonstrated that Stx1B was taken up by blood cell- and HeLa-derived EVs, an effect enhanced by chloropromazine or methyl-ß-cyclodextrin, suggesting toxin transfer within the membrane. This is a novel mechanism by which EVs derived from blood cells can sequester their toxic content, possibly to evade the host response. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

21 pages, 2151 KiB

Open AccessArticle

Metabolic Traits of Bovine Shiga Toxin-Producing Escherichia coli (STEC) Strains with Different Colonization Properties

by Stefanie A. Barth, Michael Weber, Katharina Schaufler, Christian Berens, Lutz Geue and Christian Menge

Toxins 2020, 12(6), 414; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12060414 - 22 Jun 2020

Cited by 5 | Viewed by 3063

Abstract

Cattle harbor Shiga toxin-producing Escherichia coli (STEC) in their intestinal tract, thereby providing these microorganisms with an ecological niche, but without this colonization leading to any clinical signs. In a preceding study, genotypic characterization of bovine STEC isolates unveiled that their ability to colonize cattle persistently (STEC^per) or only sporadically (STEC^spo) is more closely associated with the overall composition of the accessory rather than the core genome. However, the colonization pattern could not be unequivocally linked to the possession of classical virulence genes. This study aimed at assessing, therefore, if the presence of certain phenotypic traits in the strains determines their colonization pattern and if these can be traced back to distinctive genetic features. STEC^spo strains produced significantly more biofilm than STEC^per when incubated at lower temperatures. Key substrates, the metabolism of which showed a significant association with colonization type, were glyoxylic acid and L-rhamnose, which were utilized by STEC^spo, but not or only by some STEC^per. Genomic sequences of the respective glc and rha operons contained mutations and frameshifts in uptake and/or regulatory genes, particularly in STEC^per. These findings suggest that STEC^spo conserved features leveraging survival in the environment, whereas the acquisition of a persistent colonization phenotype in the cattle reservoir was accompanied by the loss of metabolic properties and genomic mutations in the underlying genetic pathways. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

15 pages, 486 KiB

Open AccessArticle

Pre-Harvest Survival and Post-Harvest Chlorine Tolerance of Enterohemorrhagic Escherichia coli on Lettuce

by Deepti Tyagi, Autumn L. Kraft, Sara Levadney Smith, Sherry E. Roof, Julie S. Sherwood, Martin Wiedmann and Teresa M. Bergholz

Toxins 2019, 11(11), 675; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11110675 - 19 Nov 2019

Cited by 3 | Viewed by 4666

Abstract

In the field, foodborne pathogens such as enterohemorrhagic Escherichia coli (EHEC) are capable of surviving on produce over time, yet little is known about how these pathogens adapt to this environment. To assess the impact of pre-harvest environmental conditions on EHEC survival, we quantified survival on romaine lettuce under two relative humidity (75% and 45%) and seasonal conditions (March and June). Greenhouse-grown lettuce was spray-inoculated with EHEC and placed in a growth chamber, mimicking conditions typical for June and March in Salinas Valley, California. Bacteria were enumerated on days 0, 1, 3, and 5 post-inoculation. Overall, we found that the effect of relative humidity on EHEC survival depended on the seasonal conditions. Under June seasonal conditions, higher relative humidity led to lower survival, and lower relative humidity led to greater survival, five days post-inoculation. Under March seasonal conditions, the impact of relative humidity on EHEC survival was minimal over the five days. The bacteria were also tested for their ability to survive a chlorine decontamination wash. Inoculated lettuce was incubated under the June 75% relative humidity conditions and then washed with a 50 ppm sodium hypochlorite solution (40 ppm free chlorine). When incubated under June seasonal conditions for three to five days, EHEC strains showed increased tolerance to chlorine (adj. p < 0.05) compared to chlorine tolerance upon inoculation onto lettuce. This indicated that longer incubation on lettuce led to greater EHEC survival upon exposure to chlorine. Subsequent transcriptome analysis identified the upregulation of osmotic and oxidative stress response genes by EHEC after three and five days of incubation on pre-harvest lettuce. Assessing the physiological changes in EHEC that occur during association with pre-harvest lettuce is important for understanding how changing tolerance to post-harvest control measures may occur. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

14 pages, 1015 KiB

Open AccessArticle

Epidemiology of Shiga Toxin-Producing Escherichia coli O157 in the Province of Alberta, Canada, 2009–2016

by Luiz F. Lisboa, Jonas Szelewicki, Alex Lin, Sarah Latonas, Vincent Li, Shuai Zhi, Brendon D. Parsons, Byron Berenger, Sumana Fathima and Linda Chui

Toxins 2019, 11(10), 613; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11100613 - 22 Oct 2019

Cited by 9 | Viewed by 3032

Abstract

Shiga toxin-producing Escherichia coli (STEC) infections are the product of the interaction between bacteria, phages, animals, humans, and the environment. In the late 1980s, Alberta had one of the highest incidences of STEC infections in North America. Herein, we revisit and contextualize the epidemiology of STEC O157 human infections in Alberta for the period 2009–2016. STEC O157 infections were concentrated in large urban centers, but also in rural areas with high cattle density. Hospitalization was often required when the Shiga toxin genotype stx2a stx2c was involved, however, only those aged 60 years or older and infection during spring months (April to June) independently predicted that need. Since the late 1980s, the rate of STEC O157-associated hemolytic uremic syndrome (HUS) in Alberta has remained unchanged at 5.1%, despite a marked drop in the overall incidence of the infection. While Shiga toxin genotypes stx1a stx2c and stx2a stx2c seemed associated with HUS, only those aged under 10 years and infection during spring months were independently predictive of that complication. The complexity of the current epidemiology of STEC O157 in Alberta highlights the need for a One Health approach for further progress to be made in mitigating STEC morbidity. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

11 pages, 710 KiB

Open AccessEditor’s ChoiceArticle

Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence

by Gillian A.M. Tarr, Taryn Stokowski, Smriti Shringi, Phillip I. Tarr, Stephen B. Freedman, Hanna N. Oltean, Peter M. Rabinowitz and Linda Chui

Toxins 2019, 11(10), 607; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11100607 - 18 Oct 2019

Cited by 18 | Viewed by 3821

Abstract

Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) −0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI −87.8%, −2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

17 pages, 2310 KiB

Open AccessEditor’s ChoiceArticle

Bacteriocin Occurrence and Activity in Escherichia coli Isolated from Bovines and Wastewater

by Andrew Cameron, Rahat Zaheer, Emelia H. Adator, Ruth Barbieri, Tim Reuter and Tim A. McAllister

Toxins 2019, 11(8), 475; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11080475 - 15 Aug 2019

Cited by 26 | Viewed by 5123

Abstract

The increasing prevalence of antimicrobial resistant (AMR) E. coli and related Enterobacteriaceae is a serious problem necessitating new mitigation strategies and antimicrobial agents. Bacteriocins, functionally diverse toxins produced by most microbes, have long been studied for their antimicrobial potential. Bacteriocins have once again received attention for their role as probiotic traits that could mitigate pathogen burden and AMR bacteria in livestock. Here, bacteriocins were identified by activity screening and whole-genome sequencing of bacteriocin-producers capable of inhibiting bovine and wastewater E. coli isolates enriched for resistance to cephalosporins. Producers were tested for activity against shiga toxin-producing E. coli (STEC), AMR E. coli, and related enteric pathogens. Multiple bacteriocins were found in 14 out of 90 E. coli isolates tested. Based on alignment within BACTIBASE, colicins M, B, R, Ia, Ib, S4, E1, E2, and microcins V, J25, and H47, encoded by identical, variant, or truncated genes were identified. Although some bacteriocin-producers exhibited activity against AMR and STEC E. coli in agar-based assays, most did not. Despite this idiosyncrasy, liquid co-cultures of all bacteriocinogenic isolates with luciferase-expressing generic (K12) or STEC E. coli (EDL933) resulted in inhibited growth or reduced viability. These abundant toxins may have real potential as next-generation control strategies in livestock production systems but separating the bacteriocin from its immunity gene may be necessary for such a strategy to be effective. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Graphical abstract

15 pages, 1663 KiB

Open AccessEditor’s ChoiceArticle

Virulence Characteristics and Antimicrobial Resistance Profiles of Shiga Toxin-Producing Escherichia coli Isolates from Humans in South Africa: 2006–2013

by Musafiri Karama, Beniamino T. Cenci-Goga, Mogaugedi Malahlela, Anthony M. Smith, Karen H. Keddy, Saeed El-Ashram, Lawan M. Kabiru and Alan Kalake

Toxins 2019, 11(7), 424; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11070424 - 19 Jul 2019

Cited by 23 | Viewed by 4398

Abstract

Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC O26:H11 (24%) was the most frequent serotype associated with human disease, followed by O111:H8 (16%), O157:H7 (13%) and O117:H7 (13%). The majority of isolates were positive for key virulence-associated genes including stx1 (84%), eaeA (61%), ehxA (68.4%) and espP (55%), but lacked stx2 (29%), katP (42%), etpD (16%), saa (16%) and subA (3%). stx2 positive isolates carried stx2c (26%) and/or stx2d (26%) subtypes. All pathogenicity island encoded virulence marker genes were detected in all (100%) isolates except nleA (47%), nleC (84%) and nleD (76%). Multidrug resistance was observed in 89% of isolates. PFGE revealed 34 profiles with eight distinct clusters that shared ≥80% intra-serotype similarity, regardless of the year of isolation. In conclusion, STEC isolates that were implicated in human disease between 2006 and 2013 in South Africa were mainly non-O157 strains which possessed virulence genes and markers commonly associated with STEC strains that have been incriminated in mild to severe human disease worldwide. Improved STEC monitoring and surveillance programs are needed in South Africa to control and prevent STEC disease in humans. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

37 pages, 1640 KiB

Open AccessReview

The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle

by Christian Menge

Toxins 2020, 12(9), 607; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12090607 - 21 Sep 2020

Cited by 22 | Viewed by 4914

Abstract

Many cattle are persistently colonized with Shiga toxin-producing Escherichia coli (STEC) and represent a major source of human infections with human-pathogenic STEC strains (syn. enterohemorrhagic E. coli (EHEC)). Intervention strategies most effectively protecting humans best aim at the limitation of bovine STEC shedding. Mechanisms enabling STEC to persist in cattle are only partialy understood. Cattle were long believed to resist the detrimental effects of Shiga toxins (Stxs), potent cytotoxins acting as principal virulence factors in the pathogenesis of human EHEC-associated diseases. However, work by different groups, summarized in this review, has provided substantial evidence that different types of target cells for Stxs exist in cattle. Peripheral and intestinal lymphocytes express the Stx receptor globotriaosylceramide (Gb₃syn. CD77) in vitro and in vivo in an activation-dependent fashion with Stx-binding isoforms expressed predominantly at early stages of the activation process. Subpopulations of colonic epithelial cells and macrophage-like cells, residing in the bovine mucosa in proximity to STEC colonies, are also targeted by Stxs. STEC-inoculated calves are depressed in mounting appropriate cellular immune responses which can be overcome by vaccination of the animals against Stxs early in life before encountering STEC. Considering Stx target cells and the resulting effects of Stxs in cattle, which significantly differ from effects implicated in human disease, may open promising opportunities to improve existing yet insufficient measures to limit STEC carriage and shedding by the principal reservoir host. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

52 pages, 3969 KiB

Open AccessEditor’s ChoiceReview

Molecular Biology of Escherichia coli Shiga Toxins’ Effects on Mammalian Cells

by Christian Menge

Toxins 2020, 12(5), 345; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12050345 - 23 May 2020

Cited by 37 | Viewed by 6132

Abstract

Shiga toxins (Stxs), syn. Vero(cyto)toxins, are potent bacterial exotoxins and the principal virulence factor of enterohemorrhagic Escherichia coli (EHEC), a subset of Shiga toxin-producing E. coli (STEC). EHEC strains, e.g., strains of serovars O157:H7 and O104:H4, may cause individual cases as well as large outbreaks of life-threatening diseases in humans. Stxs primarily exert a ribotoxic activity in the eukaryotic target cells of the mammalian host resulting in rapid protein synthesis inhibition and cell death. Damage of endothelial cells in the kidneys and the central nervous system by Stxs is central in the pathogenesis of hemolytic uremic syndrome (HUS) in humans and edema disease in pigs. Probably even more important, the toxins also are capable of modulating a plethora of essential cellular functions, which eventually disturb intercellular communication. The review aims at providing a comprehensive overview of the current knowledge of the time course and the consecutive steps of Stx/cell interactions at the molecular level. Intervention measures deduced from an in-depth understanding of this molecular interplay may foster our basic understanding of cellular biology and microbial pathogenesis and pave the way to the creation of host-directed active compounds to mitigate the pathological conditions of STEC infections in the mammalian body. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

46 pages, 2076 KiB

Open AccessEditor’s ChoiceReview

Shiga Toxin-Associated Hemolytic Uremic Syndrome: A Narrative Review

by Adrien Joseph, Aurélie Cointe, Patricia Mariani Kurkdjian, Cédric Rafat and Alexandre Hertig

Toxins 2020, 12(2), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12020067 - 21 Jan 2020

Cited by 120 | Viewed by 12338

Abstract

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI