Clostridium difficile and Clostridium sordellii toxins, proinflammatory versus anti-inflammatory response.
Abstract
Clostridium difficile and Clostridium sordellii produce related potent toxins (C. difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and hemorrhagic toxin (TcsH)) which belong to the large clostridial glucosylating toxin (LCGT) family. TcsL is the main C. sordellii toxin as most of toxigenic C. sordellii strains only synthesize this toxin. Intestinal colonization by C. difficile subsequently to unbalanced microbiota is accompanied by release of toxins which induce local tissue destruction and severe inflammatory response. TcdA and TcdB inactivate Rho-GTPases. Notably inactivation of RhoA results in the stimulation of the pyrin/ASC inflammasome, which is one of the main signaling pathways used by these toxins to trigger the inflammatory response. In contrast, TcsL induces an anti-inflammatory effect, mainly by inactivating Ras proteins which results in blockage of the cell cycle and killing of immune cells. The absence or moderate local inflammatory response allows C. sordellii spreading in deep tissues, production of toxin which is released in the general circulation and causes a toxic shock syndrome. The toxin mechanisms of pro-versus anti-inflammatory responses are discussed.
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In domestic or captive animal environments and in humans, the initiation of dysbiosis leading to domination by anaerobic clostridia, particularly by Clostridioides difficile, has been linked to antibiotic treatments, hospitalization, and neonatal microbiomes.
“In domestic or captive animal environments and in humans, the initiation of dysbiosis leading to domination by anaerobic clostridia, particularly by Clostridioides difficile, has been linked to antibiotic treatments, hospitalization, and neonatal microbiomes (Antharam et al., 2013;Cassir et al., 2015;Popoff, 2018).”
From Novel Lethal Clostridial Infection in Florida Manatees (Trichechus manatus latirostris): Cause of the 2013 Unusual Mortality Event in the Indian River Lagoon (2022) · cites this paper as Popoff, 2018
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Landsberg, J. H., Tabuchi, M., Rotstein, D. S., Subramaniam, K., Rodrigues, T. C. S., Waltzek, T. B., Stacy, N. I., Wilson, P. W., Kiryu, Y., Uzal, F. A., et al. (2022) · Frontiers in Marine Science · doi:10.3389/fmars.2022.841857 · Cited by 20 · see citing works
“Paeniclostridium sordellii, with the two large clostridial toxins, lethal and hemorrhagic, is usually associated with gas gangrene (myonecrosis), sepsis, or fatal toxic shock syndrome in humans (Popoff, 2018), with fewer cases restricted to intestinal disease (de la Fe et al., 2006).”
Background
- Authors
- Popoff, M. R.
- Affiliations
- Institut Pasteur (FR)
- Corresponding author
- Popoff, Michel R.
- ORCID
- Popoff, Michel R.
- Venue
- Toxicon
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 149
- Pages
- 54-64
- ISSN
- 0041-0101 (ISSN-L)
- OpenAlex
- W2769670676
- Cited by
- 23
- References
- 5
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 3
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicon (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Health Sciences › Medicine › Neurology › Botulinum Toxin and Related Neurological Disorders
- Keywords
- Clostridium difficile, Clostridium sordellii, toxin A, toxin B, lethal toxin, hemorrhagic toxin, RhoA, anti-inflammatory response, pro-inflammatory response, toxic shock syndrome, intestinal colonization, dysbiosis
- MeSH terms
- Bacterial Proteins, Bacterial Toxins, Enterotoxins, Humans, Cytokines, Clostridioides difficile, Models, Immunological, rhoA GTP-Binding Protein, Clostridium sordellii, Paraclostridium sordellii, Inflammasomes
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