Shiga Toxin

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

Deadline for manuscript submissions: closed (30 April 2011) | Viewed by 59335

Special Issue Editor


E-Mail Website
Guest Editor
Molecular Medicine Peter Gilgan Centre for Research & Learning, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada
Interests: glycosphingolipids(GSLs); GSL metabolism; GSL traffic; GSL function; shiga toxin; verotoxin cholera toxin; globotriaosylceramide; glucosylceramide; endoplasmic reticulum associated degradation (ERAD)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastrointestinal Shiga toxin (Stx) producing E. coli (STEC) infections are the major cause of the hemolytic uremic syndrome (HUS). This nephropathy remains a significant pediatric health hazard world-wide, for which there is still no specific therapy. The lack of appropriate animal models has hampered therapeutic progress. Other than age (most HUS occurs in the very young), risk factors for HUS following STEC infection have yet to de identified. Cattle provide an animal STEC reservoir and fecal contaminated foodstuffs remain the major infection source. Stx is an AB5 subunit toxin. The pentamer of (small) B subunits binding to its receptor glycosphingolipid(GSL), globotriaosyl ceramide(Gb3) in glomerular endothelial cell membranes, initiates A subunit-mediated cell death leading to HUS, but induction of inflammatory pathways is also key. Gb3 is heterogenous in its lipid structure and membrane organization, such that different Gb3 formats are differentially recognized by Stx family members, particularly Stx2, which is more frequently associated with clinical disease.

Stx binding to Gb3 also provides a biological probe of membrane GSL organization and intracellular vesicular retrograde transport. Internalization of the Stx-Gb3 complex by clathrin dependent and independent means can result in transit via endosomes, trans Golgi network and Golgi, to the endoplasmic reticulum, necessary for subunit separation and A subunit cytosolic translocation. The A subunit is an RNA glycanase which depurinates cytosolic 28S ribosomal subunits to inhibit protein synthesis. Signalling cascades which initiate apoptosis are also found downstream of Stx cell membrane Gb3 binding. The association of Gb3 with cholesterol can result in Stx binding to cell membrane lipid microdomains or rafts which is central to both signal transduction and cytotoxicity.

Stx also has antineoplastic activity due to Gb3 upregulation, and the B subunit can be used for tumour targeting.

Prof. Dr. Clifford A. Lingwood
Guest Editor

Keywords

  • hemolytic uremic syndrome
  • cytokines
  • retrograde transport
  • endothelial cells
  • glycosphingolipid

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issue

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

1383 KiB  
Article
UV-Sensitivity of Shiga Toxin-Converting Bacteriophage Virions Φ24B, 933W, P22, P27 and P32
by Sylwia Bloch, Bożena Nejman-Faleńczyk, Gracja Topka, Aleksandra Dydecka, Katarzyna Licznerska, Magdalena Narajczyk, Agnieszka Necel, Alicja Węgrzyn and Grzegorz Węgrzyn
Toxins 2015, 7(9), 3727-3739; https://doi.org/10.3390/toxins7093727 - 21 Sep 2015
Cited by 12 | Viewed by 5437
Abstract
Shiga toxin-converting bacteriophages (Stx phages) are present as prophages in Shiga toxin-producing Escherichia coli (STEC) strains. Theses phages can be transmitted to previously non-pathogenic E. coli cells making them potential producers of Shiga toxins, as they bear genes for these toxins in their [...] Read more.
Shiga toxin-converting bacteriophages (Stx phages) are present as prophages in Shiga toxin-producing Escherichia coli (STEC) strains. Theses phages can be transmitted to previously non-pathogenic E. coli cells making them potential producers of Shiga toxins, as they bear genes for these toxins in their genomes. Therefore, sensitivity of Stx phage virions to various conditions is important in both natural processes of spreading of these viruses and potential prophylactic control of appearance of novel pathogenic E. coli strains. In this report we provide evidence that virions of Stx phages are significantly more sensitive to UV irradiation than bacteriophage λ. Following UV irradiation of Stx virions at the dose of 50 J/m2, their infectivity dropped by 1–3 log10, depending on the kind of phage. Under these conditions, a considerable release of phage DNA from virions was observed, and electron microscopy analyses indicated a large proportion of partially damaged virions. Infection of E. coli cells with UV-irradiated Stx phages resulted in significantly decreased levels of expression of N and cro genes, crucial for lytic development. We conclude that inactivation of Stx virions caused by relatively low dose of UV light is due to damage of capsids that prevents effective infection of the host cells. Full article
(This article belongs to the Special Issue Shiga Toxin)
Show Figures

Graphical abstract

525 KiB  
Article
Impact of the Nature and Size of the Polymeric Backbone on the Ability of Heterobifunctional Ligands to Mediate Shiga Toxin and Serum Amyloid P Component Ternary Complex Formation
by Pavel I. Kitov, Eugenia Paszkiewicz, Joanna M. Sadowska, Zhicheng Deng, Marya Ahmed, Ravin Narain, Thomas P. Griener, George L. Mulvey, Glen D. Armstrong and David R. Bundle
Toxins 2011, 3(9), 1065-1088; https://doi.org/10.3390/toxins3091065 - 25 Aug 2011
Cited by 13 | Viewed by 9287
Abstract
Inhibition of AB5-type bacterial toxins can be achieved by heterobifunctional ligands (BAITs) that mediate assembly of supramolecular complexes involving the toxin’s pentameric cell membrane-binding subunit and an endogenous protein, serum amyloid P component, of the innate immune system. Effective in vivo [...] Read more.
Inhibition of AB5-type bacterial toxins can be achieved by heterobifunctional ligands (BAITs) that mediate assembly of supramolecular complexes involving the toxin’s pentameric cell membrane-binding subunit and an endogenous protein, serum amyloid P component, of the innate immune system. Effective in vivo protection from Shiga toxin Type 1 (Stx1) is achieved by polymer-bound, heterobifunctional inhibitors-adaptors (PolyBAITs), which exhibit prolonged half-life in circulation and by mediating formation of face-to-face SAP-AB5 complexes, block receptor recognition sites and redirect toxins to the spleen and liver for degradation. Direct correlation between solid-phase activity and protective dose of PolyBAITs both in the cytotoxicity assay and in vivo indicate that the mechanism of protection from intoxication is inhibition of toxin binding to the host cell membrane. The polymeric scaffold influences the activity not only by clustering active binding fragments but also by sterically interfering with the supramolecular complex assembly. Thus, inhibitors based on N-(2-hydroxypropyl) methacrylamide (HPMA) show significantly lower activity than polyacrylamide-based analogs. The detrimental steric effect can partially be alleviated by extending the length of the spacer, which separates pendant ligand from the backbone, as well as extending the spacer, which spans the distance between binding moieties within each heterobifunctional ligand. Herein we report that polymer size and payload of the active ligand had moderate effects on the inhibitor’s activity. Full article
(This article belongs to the Special Issue Shiga Toxin)
Show Figures

Graphical abstract

149 KiB  
Short Note
Loss of vtx Genes after the First Subcultivation Step of Verocytotoxigenic Escherichia coli O157 and Non-O157 during Isolation from Naturally Contaminated Fecal Samples
by Maria-Adelheid Joris, Karen Verstraete, Koen De Reu and Lieven De Zutter
Toxins 2011, 3(6), 672-677; https://doi.org/10.3390/toxins3060672 - 20 Jun 2011
Cited by 28 | Viewed by 6698
Abstract
Verocytotoxins VT1 and VT2, produced by Verocytotoxigenic Escherichia coli (VTEC), are encoded on temperate bacteriophages. Several studies reported the loss of the vtx genes after multiple subcultivation steps or long preservation. The objective of this study was to determine if the loss of [...] Read more.
Verocytotoxins VT1 and VT2, produced by Verocytotoxigenic Escherichia coli (VTEC), are encoded on temperate bacteriophages. Several studies reported the loss of the vtx genes after multiple subcultivation steps or long preservation. The objective of this study was to determine if the loss of the verocytotoxin genes can already occur during the first subcultivation step. Consequently, the stability of the vtx genes were tested in 40 isolates originating from 40 vtx-positive fecal samples after the first subcultivation step following the isolation procedure. The loss occurred in 12 out of 40 strains tested and was rather rare among the O157 strains compared to the non-O157 strains. This is the first study demonstrating that the loss of the verocytotoxin genes can already occur after the first subcultivation step. This may lead to an underestimation of VTEC positive samples. Full article
(This article belongs to the Special Issue Shiga Toxin)

Review

Jump to: Research, Other

257 KiB  
Review
Shiga Toxin Interaction with Human Intestinal Epithelium
by Stephanie Schüller
Toxins 2011, 3(6), 626-639; https://doi.org/10.3390/toxins3060626 - 14 Jun 2011
Cited by 93 | Viewed by 19411
Abstract
After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. [...] Read more.
After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. Furthermore, it highlights gaps in understanding that need to be addressed by future research. Full article
(This article belongs to the Special Issue Shiga Toxin)
Show Figures

Figure 1

336 KiB  
Review
Shiga Toxin: Expression, Distribution, and Its Role in the Environment
by Steven A. Mauro and Gerald B. Koudelka
Toxins 2011, 3(6), 608-625; https://doi.org/10.3390/toxins3060608 - 14 Jun 2011
Cited by 61 | Viewed by 11003
Abstract
In this review, we highlight recent work that has increased our understanding of the production and distribution of Shiga toxin in the environment. Specifically, we review studies that offer an expanded view of environmental reservoirs for Shiga toxin producing microbes in terrestrial and [...] Read more.
In this review, we highlight recent work that has increased our understanding of the production and distribution of Shiga toxin in the environment. Specifically, we review studies that offer an expanded view of environmental reservoirs for Shiga toxin producing microbes in terrestrial and aquatic ecosystems. We then relate the abundance of Shiga toxin in the environment to work that demonstrates that the genetic mechanisms underlying the production of Shiga toxin genes are modified and embellished beyond the classical microbial gene regulatory paradigms in a manner that apparently “fine tunes” the trigger to modulate the amount of toxin produced. Last, we highlight several recent studies examining microbe/protist interactions that postulate an answer to the outstanding question of why microbes might harbor and express Shiga toxin genes in the environment. Full article
(This article belongs to the Special Issue Shiga Toxin)

Other

Jump to: Research, Review

219 KiB  
Brief Report
Detection of stx1 and stx2 Genes in Pennsylvanian White-Tailed Deer
by Whitney M. Kistler, Surafel Mulugeta and Steven A. Mauro
Toxins 2011, 3(6), 640-646; https://doi.org/10.3390/toxins3060640 - 16 Jun 2011
Cited by 7 | Viewed by 6695
Abstract
Shiga toxin-producing E. coli carrying the stx1 and/or stx2 genes can cause multi-symptomatic illness in humans. A variety of terrestrial and aquatic environmental reservoirs of stx have been described. Culture based detection of microbes in deer species have found a low [...] Read more.
Shiga toxin-producing E. coli carrying the stx1 and/or stx2 genes can cause multi-symptomatic illness in humans. A variety of terrestrial and aquatic environmental reservoirs of stx have been described. Culture based detection of microbes in deer species have found a low percentage of samples that have tested positive for Stx-producing microbes, suggesting that while deer may contain these microbes, their overall abundance in deer is low. In this study, quantitative PCR (qPCR) was utilized to test for the presence of stx genes in white-tailed deer fecal matter in western Pennsylvania. In this culture independent screening, nearly half of the samples tested positive for the stx2 gene, with a bias towards samples that were concentrated with stx2. This study, while limited in scope, suggests that deer may be a greater reservoir for stx than was previously thought. Full article
(This article belongs to the Special Issue Shiga Toxin)
Show Figures

Figure 1

Back to TopTop