title: Relationship between levels of Clostridium difficile toxin A and toxin B and cecal lesions in gnotobiotic mice.
abstract: Various Clostridium difficile strains were studied with respect to their pathogenicity in monoassociated mice in relation to levels of toxin A and toxin B in vivo and in vitro. Two strains which were the most potent toxin producers in vitro induced mortality (100%); mice monoassociated with these strains were found to have high levels of both toxins in their ceca and an intense cecal epithelial ulceration together with a severe inflammatory process. No mortality was observed with the other strains. Strains which were moderately toxinogenic in vitro induced inflammation of the cecum but no ulceration, and no toxin A was found. Inflammation intensity was not related to toxin B levels. After 3 weeks, ceca returned to normal in spite of a chronic cytotoxin production. When compared with in vitro results, which showed a good correlation between the levels of the two toxins, toxin A amounts in vivo were found to be lowered relative to toxin B levels. The lack of detectable toxin A levels in animals infected with all but the two most highly toxinogenic strains prevented death. This work points out the importance of investigation of toxin A for the understanding of C. difficile pathogenicity.
authors.affiliation: Laboratoire d'Ecologie Microbienne, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
authors.forename: A
authors.initials: A
authors.lastname: Vernet
authors.forename: G
authors.initials: G
authors.lastname: Corthier
authors.forename: F
authors.initials: F
authors.lastname: Dubos-Ramaré
authors.forename: A L
authors.initials: AL
authors.lastname: Parodi
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000378:metabolism* / Q000633:toxicity; D002429:Cecal Diseases / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D002432:Cecum / Q000382:microbiology / Q000473:pathology*; D003013:Clostridium / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D006224:Cricetinae; D004768:Enterotoxins / Q000096:biosynthesis / Q000378:metabolism* / Q000633:toxicity; D005856:Germ-Free Life; D051379:Mice; D008809:Mice, Inbred C3H
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile