FIG 1.

The pathogenesis of C. difficile. C. difficile spores are ingested by hosts with altered micriobiota, where the gut microbial community is perturbed, usually due to the use of antibiotics. Once the spores are in the large intestines, several signals, including the primary bile acid cholic acid, amino acid cogerminants such as glycine, l-alanine, taurine, and l-glutamine and Ca²⁺ ions, trigger germination. After germination, adhesion of vegetative cells is mediated by C. difficile’s surface layer proteins as well as the fibronectin-binding protein and the heat shock protein GroEL. C. difficile infection is mediated by the production of its main virulence factors, namely, toxins A and B (TcdA/B) and, in some strains, the binary toxin CDT. These toxins cause disruption of the actin cytoskeleton, epithelial cell rounding, and cell death. Production of damage-associated molecular patterns (DAMPs) and several cytokines and chemokines by epithelial cells leads to the recruitment of neutrophils and other immune cells. The influx of neutrophils, along with fibrin, mucin, and cellular debris, leads to the formation of pseudomembranes, which are characteristic of C. difficile colitis.