title: Lipolysis-stimulated lipoprotein receptor (LSR) is the host receptor for the binary toxin Clostridium difficile transferase (CDT).
abstract: Clostridium difficile infection (CDI) causes antibiotic-associated diarrhea and pseudomembranous colitis. Hypervirulent strains of the pathogen, which are responsible for increased morbidity and mortality of CDI, produce the binary actin-ADP ribosylating toxin Clostridium difficile transferase (CDT) 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 lipolysis-stimulated lipoprotein receptor as the membrane receptor for CDT uptake by target cells. Moreover, we show that Clostridium perfringens iota toxin, which is a related binary actin-ADP ribosylating toxin, enters target cells via the lipolysis-stimulated lipoprotein receptor. Identification of the toxin receptors is essential for understanding of the toxin uptake and provides a most valuable basis for antitoxin strategies.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie,  Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg,  Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papatheodorou
authors.forename: Jan E
authors.initials: JE
authors.lastname: Carette
authors.forename: George W
authors.initials: GW
authors.lastname: Bell
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwan
authors.forename: Gregor
authors.initials: G
authors.lastname: Guttenberg
authors.forename: Thijn R
authors.initials: TR
authors.lastname: Brummelkamp
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D016360:Clostridioides difficile / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism*; D006238:Haploidy; D006367:HeLa Cells; D006801:Humans; D011973:Receptors, LDL / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*
chemical_list: D004768:Enterotoxins; D011973:Receptors, LDL; C035598:enterotoxin, Clostridium; C085992:lipolysis-stimulated receptor; D014166:Transferases