Identification of the host cell receptor of Clostridium difficile toxin CDT

The human enteric pathogen Clostridium difficile is the most serious cause of antibiotic-associated diarrhea and pseudomembranous colitis. Hypervirulent strains of the pathogen, associated with more severe disease and increased death rates, produce the binary actin-ADP-ribosylating toxin CDT (Clostridium difficile transferase) in addition to the Rho glucosylating toxins A and B. CDT depolymerizes the actin cytoskeleton, increases adherence and colonization of Clostridia by induction of microtubule-based cell protrusions and, eventually, causes death of target cells. Using a haploid genetic screen, we identified the host cell receptor for binding and uptake of CDT by target cells. In addition, we present evidence that C. perfringens iota toxin, a related binary actin-ADP-ribosylating toxin, shares the same membrane receptor as CDT for cell entry. Identification of the host cell receptor of CDT provides a valuable basis for the development of new therapeutic strategies against CDT and related toxins.