1. Alteraciones de las adhesiones celulares por las toxinas de Clostridioides difficile y Paeniclostridium sordellii.
- Author
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Quesada-Gómez, Carlos
- Subjects
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TOXIC shock syndrome , *SPOREFORMING bacteria , *BACTERIAL toxins , *BACTERIAL adhesion , *CELL junctions , *CELL adhesion - Abstract
Introduction: Clostridiodes difficile and Paeniclostridium sordellii are Gram-positive, anaerobic and sporeforming bacteria. C. difficile is the leading cause of antibiotic-associated diarrea and P. sordellii is mainly reported in infections in pregnant women with toxic shock syndrome and in other infections in animals. Glycosyltransferase toxins are the main virulence factors of both bacteria, C. difficile produces toxins A and B (TcdA and TcdB) while P. sordelli produces lethal (TcsL) and hemorrhagic (TcsH) toxins. Objective: To provide a description of the mechanisms of action on cell adhesions of bacterial toxins with glycosyltransferase activity and their association with infections produced by C. difficile and P. sordellii. Methods: A review was carried out which sought to meet the following parameters: Only experimental articles published between 2000 and 2021 in Spanish or English language. These articles were obtained from Google Scholar, Science Direct and Pubmed databases. Furthermore, the following keywords were included: Clostridium difficile, Clostridium sordellii, Clostridiodes, Paeniclostridium, cellular adhesion (focal, tight-adhesion), or toxins. Results: TcdA, TcdB, TcsL and TcsH belong to the family of large glycosylating toxins, which have glycosiltransferase activity over monomeric GTPases. Eukaryotic cells maintain their structure and conformation thanks to cell adhesions, which include focal (extracellular cell-matrix) and tight (cell-cell) adhesion. The mechanism of action of these clostridial toxins is that they alter focal adhesion proteins such as Src, FAK, and paxillin, and for tight adhesion such as ZO1, occludins, and the E-cadherin-catenin complex. This is due to mechanisms dependent on the glycosylation of GTPases and others that are not. The alteration of these adhesions interferes with the correct function of the epithelial barrier. As a result of these alterations induced by C. difficile toxins in eukaryotic cell junctions, a disruption of the intestinal epithelial barrier, increased inflammation, and permeability are observed, which exacerbates the clinical symptoms with complications such as pseudomembranous colitis. P. sordellii mainly affects the pulmonary epithelium, by increasing its vascular permeability allowing the passage of fluids to the lung parenchyma, leading to anoxia and even death by altering cellular adhesions. Conclusion: The information available is not comprehensive, a fact that emphasize the importance to continue researching on the subject. It is still unknown whether there are other proteins that are altered, as well as the mechanism by which they are altered. The study of different TcdBs is important due to the high variability of strains, which influences their expression, their specificity as a substrate or receptor, among other important aspects in the pathogenesis of this disease. All this to better understand the pathogenesis of clinical pictures by bacteria producing large clostridial toxins with glycosyltransferase activity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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