Adhesion of enterotoxigenic Escherichia coli in humans and animals.

Abstract

Enterotoxigenic Escherichia coli (ETEC), an important cause of diarrhoea in humans and animal, require accessory virulence properties in addition to enterotoxin to manifest virulence. Several classes of pili (hair-like protein surface organelles) promote adhesion of ETEC to small intestinal mucosa. Antibody directed against adhesion pili interferes with colonization of the small intestine and prevents disease. This paper reviews studies with purified K88, K99 and 987 type pili used as parenteral vaccines in pregnant pigs and cattle. Infant animals suckled on immunized mothers were significantly protected against fatal disease. Colonization factor antigen (CFA) I and II pili, and type 1 somatic pili, promote adhesion of human ETEC pathogens to epithelial cells in vitro and are generally recognized as accessory virulence factors. CFA/I and II were found in only 25% of 36 human ETEC infections; positive strains were usually LT+/ST+ (LT: heat-labile; ST: heat-stable). Strains lacking CFA/I and II are virulent; other factors must be responsible for adhesion in such strains. While none of 14 LT+/ST- strains elaborated CFA/I or II, 10 (71%) possessed type 1 somatic pili. An initial ETEC diarrhoeal infection in volunteers stimulated protective immunity against diarrhoea on re-challenge with the same strain. Despite clinical protection healthy "veterans" excreted the ETEC strain to the same degree as ill controls. Thus the mechanisms of immunity was not bactericidal. Disease-induced LT antitoxic immunity failed to protect volunteers against challenge with a heterologous (LT+/ST-) strain. One explanation of these observations is that the mechanism of protection was anti-adhesive with antibody directed against adhesive factors on the bacterial surface preventing attachment of bacteria to receptors on small intestinal mucosal cells. Immunoprophylaxis against ETEC in humans with purified pili vaccines appears feasible.