Alterations in cell adhesions by Clostridiodes difficile and Paeniclostridium sordellii toxins

Abstract

Introduction: Clostridiodes difficile and Paeniclostridium sordellii are Gram-positive, anaerobic and spore-forming 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 toxin (TcsL) and hemorrhagic toxin (TcsH). 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. Methodology: A review was carried out which sought to meet the following parameters: Only experimental articles published between 2000 and 2021 in the Spanish or English. 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 ZO-1, 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, there is a disruption of the intestinal epithelial barrier, increased inflammation, and permeability, which exacerbates the clinical symptoms, with complications such as pseudomembranous colitis. P. sordellii it mainly affects the pulmonary epithelium, by increasing its vascular permeability, it allows the passage of fluids to the lung parenchym, leading to anoxia and even death by altering cellular adhesions. Conclusion: The information available is not so comprehensive so it is important to continue research on the subject. It is still unknown whether there are other proteins that are altered, as well as the mechanism by which they alter. 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 in order to better understand the pathogenesis of clinical pictures by bacteria producing large clostridial toxins with glycosyltransferase activity.