Relationship between levels of Clostridium difficile toxin A and toxin B and cecal lesions in gnotobiotic mice

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.