Shiga Toxin-Associated Infection

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

Deadline for manuscript submissions: closed (31 August 2018)

Special Issue Information

Dear Colleagues,

Shiga toxin-associated infection is a major threat to public health, leading to watery or bloody diarrhea and the severe, and sometimes life-threatening, complication termed hemolytic uremic syndrome. Hemolytic uremic syndrome is characterized by the post-diarrheal acute onset of hemolytic anemia, thrombocytopenia and kidney failure. Extra-renal manifestations may include major neurological complications, as well as injury to multiple organs. Hemolytic uremic syndrome has been strongly associated with clinical isolates of enterohemorrhagic Escherichia coli or Shigella dysentriae that produce the unique virulence factor Shiga toxin.

Shiga toxin-producing bacteria may contaminate food and water. Upon ingestion, the bacteria can interact with commensal strains and colonize the intestine. The release of Shiga toxin enables its binding to a glycolipid receptor on host cells. Advanced studies have demonstrated the mechanism of toxin uptake by endocytosis and its retrograde transport to ribosomes. The cytotoxic effects are associated with ribosome inactivation thereby inhibiting protein synthesis and leading to cell death. In addition, activation of cellular stress signals may trigger apoptosis as well as the host response. Emerging evidence suggests that the toxin circulates bound to blood cells and in blood cell-derived microvesicles, thereby reaching its target organs, such as the kidney. Cell death and activation of the host response, including the onset of thrombosis, may contribute to features of hemolytic uremic syndrome.

This Special Issue of Toxins is dedicated to various features of Shiga toxin-associated infection, from food safety to cellular and animal models of infection as well as the pathophysiology of human infection. Aspects of prevention, management and potential therapeutic developments will be addressed.

Manuscript Submission Information

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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

  • verotoxin
  • hemolytic uremic syndrome
  • hemorrhagic colitis
  • food safety
  • enterohemorrhagic Escherichia coli

Published Papers (1 paper)

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Research

20 pages, 8463 KiB  
Article
Structural Basis for the Specific Neutralization of Stx2a with a Camelid Single Domain Antibody Fragment
by Robert Alvin Bernedo-Navarro, Ema Romão, Tomomasa Yano, Joar Pinto, Henri De Greve, Yann G.-J. Sterckx and Serge Muyldermans
Toxins 2018, 10(3), 108; https://doi.org/10.3390/toxins10030108 - 01 Mar 2018
Cited by 16 | Viewed by 5771
Abstract
Background: Shiga toxin-producing Escherichia coli (STEC) are a subset of pathogens leading to illnesses such as diarrhea, hemolytic uremic syndrome and even death. The Shiga toxins are the main virulence factors and divided in two groups: Stx1 and Stx2, of which the latter [...] Read more.
Background: Shiga toxin-producing Escherichia coli (STEC) are a subset of pathogens leading to illnesses such as diarrhea, hemolytic uremic syndrome and even death. The Shiga toxins are the main virulence factors and divided in two groups: Stx1 and Stx2, of which the latter is more frequently associated with severe pathologies in humans. Results: An immune library of nanobodies (Nbs) was constructed after immunizing an alpaca with recombinant Shiga toxin-2a B subunit (rStx2aB), to retrieve multiple rStx2aB-specific Nbs. The specificity of five Nbs towards rStx2aB was confirmed in ELISA and Western blot. Nb113 had the highest affinity (9.6 nM) and its bivalent construct exhibited a 100-fold higher functional affinity. The structure of the Nb113 in complex with rStx2aB was determined via X-ray crystallography. The crystal structure of the Nb113–rStx2aB complex revealed that five copies of Nb113 bind to the rStx2aB pentamer and that the Nb113 epitope overlaps with the Gb3 binding site, thereby providing a structural basis for the neutralization of Stx2a by Nb113 that was observed on Vero cells. Finally, the tandem-repeated, bivalent Nb1132 exhibits a higher toxin neutralization capacity compared to monovalent Nb113. Conclusions: The Nb of highest affinity for rStx2aB is also the best Stx2a and Stx2c toxin neutralizing Nb, especially in a bivalent format. This lead Nb neutralizes Stx2a by competing for the Gb3 receptor. The fusion of the bivalent Nb1132 with a serum albumin specific Nb is expected to combine high toxin neutralization potential with prolonged blood circulation. Full article
(This article belongs to the Special Issue Shiga Toxin-Associated Infection)
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