Invasive Bacterial Pathogens of the Intestine: Shigella Virulence Plasmids and Potential Vaccine Approaches

Abstract

Bacterial diseases of the gastrointestinal tract usually occur by one of three overall mechanisms. The first mechanism, termed “intoxication,” occurs by bacterial secretion of an exotoxin that oftentimes is preformed in food prior to ingestion by the host. This process is exemplified by staphylococcal or clostridial food poisoning. In contrast, the remaining two processes require living and multiplying disease agents. In the “enterotoxigenic” mechanism, as discussed elsewhere in this volume, bacteria colonize the small intestine, usually in the jejunum or duodenum. These bacteria multiply on the intestinal surface and elaborate an enterotoxin that stimulates excessive fluid and electrolyte efflux resulting in a watery diarrhea. Enteropathogenic Escherichia coli and Vibrio cholera serve as typical examples. Finally, a third group of organisms, termed “invasive,” actually penetrate the epithelial mucosa of the large intestine. Subsequently, these organisms multiply intracellularly and disseminate within or through the mucosa. This latter mechanism, classically typified by Shigella and Salmonella, is now thought to be used by invasive strains of 15. coli, Yersinia, and, possibly, Campylobacter. In contrast to other invasive bacterial diseases like salmonellosis in which the invading bacteria are disseminated throughout the host, shigellosis is a disease normally confined to the intestinal lining. Whereas toxigenic organisms generally require a large dose of organisms to cause disease, previous studies have shown that as few as ten virulent cells of Shigella can cause disease in humans. Thus, these features distinquish the toxigenic from the invasive mechanism of intestinal disease (see reviews^l,2).