Clostridioides difficile toxins (TcdA and TcdB) (C. diff toxins)

Clostridioides difficile is a Gram-positive, spore-forming anaerobic bacterium that is the primary cause of antibiotic-associated colitis (StatPearls, 2023). The disease is driven by the production of two large clostridial toxins, TcdA and TcdB, which act as glucosyltransferases to inactivate host Rho-family GTPases like Rho, Rac, and Cdc42 (Nature Reviews Microbiology, 2016). This molecular disruption causes the collapse of the actin cytoskeleton in colonic epithelial cells, leading to cell death, loss of intestinal barrier integrity, and severe inflammation (NIH, 2022). Therapeutic strategies involve eradicating the vegetative bacteria with antibiotics such as vancomycin or fidaxomicin, or neutralizing the toxins directly using the monoclonal antibody bezlotoxumab (FDA, 2016). Because the infection typically occurs after the native intestinal microbiota is depleted, restoring the microbiome through fecal microbiota transplantation (FMT) has become a standard of care for recurrent cases to restore colonization resistance (Clinical Infectious Diseases, 2021). The interplay between the bacterium, its toxins, and the host's microbial environment defines the clinical progression and treatment success of the infection.

Other names

Clostridium difficileC. diffTcdATcdBEnterotoxin ACytotoxin BC. difficile toxins

Inhibition of bacterial cell wall synthesis (vancomycin), inhibition of bacterial RNA polymerase (fidaxomicin), neutralization of bacterial exotoxin B (bezlotoxumab), and restoration of intestinal microbial diversity to provide colonization resistance (FMT).