Toxin release mediated by the novel autolysin Cwp19 in Clostridium difficile

Clostridium difficile, also known as Clostriodioides difficile, is a Gram positive, spore-forming bacterium and a leading cause of antibiotic-associated diarrhea in nosocomial environments. The key virulence factors of this pathogen are two toxins, toxin A and toxin B, released from the cells to the gut and causing colonic injury and inflammation. Although their mechanism of action is well known, the toxins A and B have no peptide signals and their secretion mechanisms involving the holin-like protein TcdE and autolysis are still under active investigation. Autolysis is primarily mediated by peptidoglycan hydrolases, an important group of enzymes that cleave covalent bonds in the cell wall peptidoglycan. Peptidoglycan hydrolases are essential for peptidoglycan remodeling but most of them also have the potential to lyse the cells under various conditions. In a recent report by Wydau-Dematteis et al. (MBio 9(3): e00648-18), we characterized a novel peptidoglycan hydrolase Cwp19 in C. difficile. Importantly, Cwp19 mediates toxins secretion in a glucose-dependent fashion suggesting a potential role in C. difficile pathogenesis. Peptidoglycan hydrolases are not very well characterized in C. difficile despite the important role of these enzymes in cell division and sporulation as shown in model organisms like Bacillus subtilis. In addition, these enzymes can be implicated in pathogenicity as exemplified by the release of pneumococcal virulence factors.