title: Identification of the cellular receptor of Clostridium spiroforme toxin.
abstract: 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 production 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.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papatheodorou
authors.forename: Claudia
authors.initials: C
authors.lastname: Wilczek
authors.forename: Thilo
authors.initials: T
authors.lastname: Nölke
authors.forename: Gregor
authors.initials: G
authors.lastname: Guttenberg
authors.forename: Daniel
authors.initials: D
authors.lastname: Hornuss
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwan
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D001410:Bacillus megaterium / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D001905:Botulinum Toxins / Q000378:metabolism; D018938:Caco-2 Cells; D002460:Cell Line; D016360:Clostridioides difficile / Q000201:enzymology; D003013:Clostridium / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D003015:Clostridium Infections / Q000473:pathology; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D011973:Receptors, LDL; D011994:Recombinant Proteins; C050737:iota toxin, Clostridium perfringens; C054948:iota toxin, Clostridium spiroforme; C085992:lipolysis-stimulated receptor; D036002:ADP Ribose Transferases; D001905:Botulinum Toxins; C096324:botulinum toxin type C