C. diff Toxin A

C. difficile toxin A is a toxin produced by C. difficile. It is similar to C. difficile toxin B. Toxins act by destroying the intestinal mucosa and cause symptoms of C. difficile infection, including pseudomembranous colitis. TcdA is one of the largest known bacterial toxins. The molecular weight is 308 kDa and is usually described as an effective enterotoxin, but it also has some cytotoxic activity. Toxins act by glucosylation to modify host cell GTPase proteins, resulting in changes in cellular activity. Risk factors for C. difficile infection include antibiotic treatment, which can destroy the normal gut microbiota and cause colonization of C. difficile bacteria. TcdA must be internalized into host cells by endocytosis to obtain a cytosol. Receptor binding is the first step required to enter a cell by endocytosis in acidic endosomes. Low pH in the endosomes induce structural changes, such as exposure to hydrophobic domains, which are critical for TcdA function. Actoxumab is a human monoclonal antibody used to prevent recurrence of C. difficile infection. The drug, along with bezlotoxumab, was developed through a phase II trial of Medarex in collaboration with MassBiologics of the University of Massachusetts Medical School.