Identification of the cellular receptor of Clostridium spiroforme toxin

Clostridium spiroforme produces the binary actin-ADP-ribosylating toxin CST (C. spiroforme toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant pro-duction of the enzyme component (CSTa) and the binding component (CSTb) of C. spiroforme toxin in Bacillus megaterium. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins Clostridium difficile transferase (CDT) and Clostridium perfringens iota toxin. Microscopic studies revealed that CST, but not the related Clostridium botulinum C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor. Clostridium spiroforme is frequently found in the digestive tractsof rabbits, where it is proposed to be responsible for severe diarrhea, enterocolitis, and eventually death of the host (7). The virulence of C. spiroforme strongly correlates with the production of an enterotoxin termed CST (C. spiroforme toxin) (6) that be-longs to the family of clostridial iota-like binary toxins, including C. perfringens iota toxin and C. difficile transferase (CDT). CST is an A-B-type toxin, with an enzyme component (CSTa) harborin