Virulence Factors of Clostridium difficile and Its Pathogenesis in Intestinal Infection in Man

Abstract

Clostridium difficile was isolated in 1935 by Hall and O'Toole (29) from the feces of healthy neonate, and the microorganism was first designated Bacillus difficilis. The 'difficilis' was originated from the difficulty in cultivation of the microorganism. They showed that the microorganism had lethality to rabbit or guinea pig and edema-inducing activity. Later the microorganism was classified as Clostridium difficile in 1938 by Prevot (71) . The pathogenicity of C. difficile to human had not been reported until when association of C. difficile with human pseudomembranous colitis (PMC) was demonstrated in 1978. In 1893, Finney (19) first reported an occurrence of PMC in the patient with peptic ulcer after gastroenterostomy. The number of cases with PMC increased in parallel to an increase of use of antibiotics in the 1970s. Although Staphylococcus aureus was speculated to be a causative agent for PMC, there was no determinative evidence for the hypothesis. In 1977, Larson et al (48) reported that clostridial toxin was causative agent for PMC, and in 1978 toxigenic C. difficile was identified as a cause of PMC by Bartlett et al (3), George et al (23) and Larson et al (49) . The isolation rate of C. difficile from feces of healthy adults was 0-12.8%, and that of the patients with PMC was 80-100% (59) . It is considered that change of intestinal flora by administration of antimicrobial agent and following selection of toxin-producing C. difficile are background for the occurrence of PMC. Virulence factors of C. difficile and its pathogenesis in intestinal infection in man are discussed in this review by indicating not only previous reports in the literature but also our own experimental data.