DEVELOPMENT OF AN IMPROVED ANIMAL-MODEL OF SHIGELLOSIS IN THE ADULT-RABBIT BY COLONIC INFECTION WITH SHIGELLA-FLEXNERI 2A

Rabbits are not usually susceptible to intestinal Shigella infection w ithout extensive pretreatment, including starvation and administration of antimicrobial, antimotility, and toxic agents (carbon tetrachlorid e). Most animals infected this way die rapidly and do not always devel op colonic lesions and signs of dysentery, We describe here a successf ul experimental infection in the adult rabbit which does not require p reparatory treatment and which reproduced characteristic features of h uman shigellosis, Unstarved, untreated adult rabbits were infected by direct inoculation of virulent Shigella flexneri 2a (10 ml of 10(7) ba cteria per ml) into the proximal colon after ligation of the distal ce cum (cecal bypass). Within 24 h of infection, most inoculated animals consistently developed clinical dysentery, characterized by liquid sto ol mixed with mucus and blood, leukocytosis, anorexia, and weight loss , Histologically, there were edema, exudation, superficial ulceration, and polymorphonuclear infiltrations in the lamina propria; crypt absc ess formation; focal hemorrhages; and the presence of immunohistochemi cally stained S. flexneri in the colonic mucosa, Successful bacterial colonization was indicated by the isolation of the challenge strain of S. flexneri 2a from the colonic contents. None of the control rabbits challenged with nonvirulent S. flexneri or without cecal bypass devel oped dysentery or colitis. We conclude that successful Shigella infect ion can be induced by direct colonic inoculation with virulent S. flex neri 2a in adult rabbits without starvation and pretreatment. The coli tis is dependent on the virulence of the bacteria and on the cecal byp ass, This model should be useful in studies of the immunopathogenesis of Shigella infection.