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Toxins
Special Issues
Clostridium difficile Toxins
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Clostridium difficile Toxins

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 3348

Special Issue Editor

Prof. Dr. Jason L. Larabee

E-Mail Website
Guest Editor
Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Interests: bacterial toxins; Clostridioides difficile; SARS-CoV-2; host responses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

Clostridioides difficile is a Gram-positive bacterium causing enteric disease mostly under clinical conditions involving antibiotic treatment. Disease manifestations are coupled to the actions of secreted proteinaceous toxins exemplified by TcdB, which is a large multidomain toxin that enters host cells and glucosylates small GTPases. Other toxins produced by C. difficile include TcdA, which is another large clostridial toxin homologous to TcdB, and binary toxin (CDT), which lacks TcdB homology and consists of a subunit with ribosyltransferase activity (CDTa) and a separate subunit with pore-forming activity (CDTb). Disease-causing strains of C. difficile vary in their toxin repertoire but usually possess TcdB. Recent work within this field has explored the complex landscape of toxin receptors and has begun to address how variant toxins alter disease trajectory. The aim of this Special Issue is to build on these recent advances in order to better understand the mechanism of action of C. difficile toxins.

Prof. Dr. Jason L. Larabee
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

  • C. difficile
  • C. difficile toxins
  • TcdB
  • TcdA
  • binary toxin

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Published Papers (1 paper)

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Research

19 pages, 2492 KiB  
Article
A Highly Specific Holin-Mediated Mechanism Facilitates the Secretion of Lethal Toxin TcsL in Paeniclostridium sordellii
by Callum J. Vidor, Audrey Hamiot, Jessica Wisniewski, Rommel A. Mathias, Bruno Dupuy, Milena Awad and Dena Lyras
Toxins 2022, 14(2), 124; https://doi.org/10.3390/toxins14020124 - 8 Feb 2022
Cited by 6 | Viewed by 2726
Abstract
Protein secretion is generally mediated by a series of distinct pathways in bacteria. Recently, evidence of a novel bacterial secretion pathway involving a bacteriophage-related protein has emerged. TcdE, a holin-like protein encoded by toxigenic isolates of Clostridioides difficile, mediates the release of [...] Read more.
Protein secretion is generally mediated by a series of distinct pathways in bacteria. Recently, evidence of a novel bacterial secretion pathway involving a bacteriophage-related protein has emerged. TcdE, a holin-like protein encoded by toxigenic isolates of Clostridioides difficile, mediates the release of the large clostridial glucosylating toxins (LCGTs), TcdA and TcdB, and TpeL from C. perfringens uses another holin-like protein, TpeE, for its secretion; however, it is not yet known if TcdE or TpeE secretion is specific to these proteins. It is also unknown if other members of the LCGT-producing clostridia, including Paeniclostridium sordellii (previously Clostridium sordellii), use a similar toxin-release mechanism. Here, we confirm that each of the LCGT-producing clostridia encode functional holin-like proteins in close proximity to the toxin genes. To characterise the respective roles of these holin-like proteins in the release of the LCGTs, P. sordellii and its lethal toxin, TcsL, were used as a model. Construction and analysis of mutants of the P. sordellii tcsE (holin-like) gene demonstrated that TcsE plays a significant role in TcsL release. Proteomic analysis of the secretome from the tcsE mutant confirmed that TcsE is required for efficient TcsL secretion. Unexpectedly, comparative sample analysis showed that TcsL was the only protein significantly altered in its release, suggesting that this holin-like protein has specifically evolved to function in the release of this important virulence factor. This specificity has, to our knowledge, not been previously shown and suggests that this protein may function as part of a specific mechanism for the release of all LCGTs. Full article
(This article belongs to the Special Issue Clostridium difficile Toxins)
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