Clostridioides difficile (formerly named Clostridium difficile) is the dominant causative agent of a spectrum of illnesses, which frequently occur as the consequence of antibiotic treatment of patients. C. difficile infections (CDIs) cause mild to severe diarrhea (so-called antibiotic-associated diarrhea) but also pseudomembranous enterocolitis with complications like toxic megacolon, bowel perforation, and death. Three protein toxins are involved in the pathology of CDIs, toxin A (TcdA) and toxin B (TcdB), which are the prototypes of large clostridial glucosylating toxins, and C. difficile ADP-ribosyltransferase CDT.