Pathogenesis of {Shigella} dysenteriae 1 ({Shiga}) {Dysentery}

The Shiga bacillus is exceptional among enteric pathogens in possessing two potential pathogenetic modes of action, invasiveness and enterotoxin. The role of each was investigated. ,Two fully virulent (invasive toxigenic) and two modified (noninvasive toxigenic and invasive nontoxigenic) Shiga strains were defined in animal and in-vitro models. The virulent strains produced disease in volunteers in doses as low as 101 organisms. Illness was characterized by fever, short-lived diarrhea, and passage of scanty stools of blood and mucus. During illness, the pathogen was isolated from one of 16 samples of small-intestinal contents, and free toxin could not be demonstrated. Concomitantly, large numbers of Shiga organisms were excreted in stool. The major lesions were in the large bowel where clinical colitis was confirmed by proctoscopy and biopsy. Large numbers of a noninvasive toxigenic strain (106−1011 organisms) were well tolerated by 85 of 86 men. One volunteer had dysentery after the organism had reverted to an invasive form. In contrast, an invasive nontoxigenic strain caused shigellosis in monkeys and volunteers. Epithelial penetration is the cardinal virulence property of Shigella dysenteriae 1. The role of Shiga toxin in human disease remains to be defined.