title: Lethal toxin is a critical determinant of rapid mortality in rodent models of Clostridium sordellii endometritis.
abstract: The toxigenic anaerobe Clostridium sordellii is an uncommon but highly lethal cause of human infection and toxic shock syndrome, yet few studies have addressed its pathogenetic mechanisms. To better characterize the microbial determinants of rapid death from infection both in vitro and in vivo studies were performed to compare a clinical strain of C. sordellii (DA-108), isolated from a patient who survived a disseminated infection unaccompanied by toxic shock syndrome, to a virulent reference strain (ATCC9714). Rodent models of endometrial and peritoneal infection with C. sordellii ATCC9714 were rapidly lethal, while infections with DA-108 were not. Extensive genetic and functional comparisons of virulence factor and toxin expression between these two bacterial strains yielded many similarities, with the noted exception that strain DA-108 lacked the tcsL gene, which encodes the large clostridial glucosyltransferase enzyme lethal toxin (TcsL). The targeted removal by immunoprecipitation of TcsL protected animals from death following injection of crude culture supernatants from strain ATCC9714. Injections of a monoclonal anti-TcsL IgG protected animals from death during C. sordellii ATCC9714 infection, suggesting that such an approach might improve the treatment of patients with C. sordellii-induced toxic shock syndrome.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Yibai
authors.initials: Y
authors.lastname: Hao
authors.forename: Tennille
authors.initials: T
authors.lastname: Senn
authors.forename: Judy S
authors.initials: JS
authors.lastname: Opp
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.forename: Teri
authors.initials: T
authors.lastname: Thiele
authors.forename: Geetha
authors.initials: G
authors.lastname: Srinivas
authors.forename: Steven K
authors.initials: SK
authors.lastname: Huang
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
mesh_terms: D000818:Animals; D000992:Antitoxins / Q000008:administration & dosage; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000633:toxicity*; D003015:Clostridium Infections / Q000382:microbiology* / Q000401:mortality* / Q000517:prevention & control; D047989:Paraclostridium sordellii / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D004716:Endometritis / Q000382:microbiology* / Q000401:mortality* / Q000517:prevention & control; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D037521:Virulence Factors / Q000235:genetics / Q000633:toxicity
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D007074:Immunoglobulin G; D037521:Virulence Factors; C072292:lethal toxin LT, Clostridium sordellii