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Special Issue "Heat-Stable Enterotoxins"

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

Deadline for manuscript submissions: 15 November 2017

Special Issue Editor

Guest Editor
Prof. Dr. Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics, Division of Clinical Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Website | E-Mail
Interests: guanylate cyclase C in health and disease

Special Issue Information

Dear Colleagues,

Diarrheagenic bacterial heat-stable enteroxins (STs) are a major cause of morbidity and mortality worldwide. This family of homologous toxins induces diarrhea by recapitulating the structure of the endogenous intestinal paracrine hormones guanylin and uroguanylin. This molecular mimicry confers on STs the ability to co-opt signaling through the intestinal receptor guanylate cyclase C (GCC), which regulates epithelial fluid and electrolyte balance. Beyond secretion, GCC and its cognate ligands have emerged as important regulators of fundamental homeostatic processes which organize the intestinal crypt-surface axis. Moroever, dysregulation of this signaling system plays a key role in pathophysiological processes beyond infectious diarrhea, including intestinal transformation, mucosal inflammation, and gut–brain satiety signaling. Understanding the normal function of the GCC signaling axis, and mechanisms underlying its pathophysiological disruption, provides unique opportunities to create therapeutic solutions using toxins and their cognate receptors for major diseases including infectious diarrhea, chronic constipation, colorectal cancer, inflammatory bowel disease and obesity.

Prof. Dr. Scott A. Waldman
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 papers will be 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 single-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 1500 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

  • heat-stable enterotoxins;
  • guanylate cyclase C;
  • guanylin;
  • uroguanylin;
  • secretory diarrhea;
  • chronic constipation;
  • colorectal cancer;
  • irritable bowel syndrome (constipation type);
  • inflammatory bowel disease;
  • obesity

Published Papers (4 papers)

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Research

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Open AccessFeature PaperArticle ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice
Toxins 2017, 9(9), 279; doi:10.3390/toxins9090279
Received: 15 August 2017 / Revised: 31 August 2017 / Accepted: 6 September 2017 / Published: 12 September 2017
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Abstract
There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries,
[...] Read more.
There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
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Open AccessArticle Reduced Enterotoxin D Formation on Boiled Ham in Staphylococcus aureus Δagr Mutant
Toxins 2017, 9(9), 263; doi:10.3390/toxins9090263
Received: 4 August 2017 / Revised: 21 August 2017 / Accepted: 24 August 2017 / Published: 25 August 2017
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Abstract
Staphylococcal food poisoning (SFP) is a common cause of foodborne illness worldwide, and enterotoxin D (SED) is one of the most frequent Staphylococcus aureus enterotoxins associated with it. It has been reported that the expression and formation of SED in S. aureus is
[...] Read more.
Staphylococcal food poisoning (SFP) is a common cause of foodborne illness worldwide, and enterotoxin D (SED) is one of the most frequent Staphylococcus aureus enterotoxins associated with it. It has been reported that the expression and formation of SED in S. aureus is regulated by the quorum sensing Agr system. In this study, the effect of agr deletion on sed expression in S. aureus grown on boiled ham was investigated. Growth, sed mRNA and SED protein levels in an S. aureus wild type strain and its isogenic Δagr mutant were monitored for 14 days at 22 °C. The results showed that although deletion of the agr gene did not affect the growth rate or maximum cell density of S. aureus on boiled ham, it had a pronounced effect on SED formation during the first 5 days of incubation. The SED concentration was not reflected in the amount of preceding sed transcripts, suggesting that sed transcription levels may not always reflect SED formation. The expression of RNAIII transcript, the regulatory signal of the Agr system, was also monitored. Similar transcription patterns were observed for RNAIII and sed. Surprisingly, in the Δagr mutant, sed expression was comparable to that in the wild type strain, and was thus unaffected by deletion of the Agr system. These results demonstrate that the Agr system appears to only partially affect SED formation, even in a real food environment. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
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Open AccessArticle Interaction between Various Apple Procyanidin and Staphylococcal Enterotoxin A and Their Inhibitory Effects on Toxin Activity
Toxins 2017, 9(8), 243; doi:10.3390/toxins9080243
Received: 30 June 2017 / Revised: 3 August 2017 / Accepted: 4 August 2017 / Published: 7 August 2017
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Abstract
In this study, we investigated the interaction between apple polyphenols (AP; mainly consisting of procyanidin (PC) from an apple) and staphylococcal enterotoxin A (SEA), and the inhibitory effects of AP on SEA activity. According to the degree of polymerization, in particularly highly polymerized
[...] Read more.
In this study, we investigated the interaction between apple polyphenols (AP; mainly consisting of procyanidin (PC) from an apple) and staphylococcal enterotoxin A (SEA), and the inhibitory effects of AP on SEA activity. According to the degree of polymerization, in particularly highly polymerized PC (more than pentamer) strongly interacted with SEA. The binding affinity of AP with SEA molecules was determined using Biacore analysis. AP reacted with SEA immobilized on a Biacore sensor chip. After treatment with pepsin and pancreatin, to examine the changes of binding affinity of AP in intragastric conditions, AP maintained interaction with SEA. We examined whether AP inhibits the proliferation and interferon-γ (IFN-γ) production induced by SEA in mouse spleen cells. AP strongly inactivated the proliferation and IFN-γ production induced by SEA. These results suggest that AP, which has a higher degree of polymerization, inactivates stronger biological activity of SEA through interaction with SEA. Our studies are the first to demonstrate the relationship between the degree of polymerization of AP and the inhibitory effects on SEA activities. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
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Review

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Open AccessFeature PaperReview The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, as a Pharmacological Target in Colorectal Cancer Immunotherapy: A Bench-to-Bedside Current Report
Toxins 2017, 9(9), 282; doi:10.3390/toxins9090282
Received: 15 August 2017 / Revised: 5 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
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Abstract
Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient
[...] Read more.
Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient population while sparing healthy tissue from damaging autoimmunity. The intestinally restricted receptor guanylyl cyclase C (GUCY2C) is a target that has been investigated for the treatment of colorectal cancer and numerous animal, and clinical studies have demonstrated both efficacy and safety. Here, we describe the current state of GUCY2C-directed cancer immunotherapy and the future directions of this work. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
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