Role of the K88 Antigen in the Pathogenesis of Neonatal Diarrhea Caused by Escherichia coli in Piglets

Abstract

The role of the K88 antigen of Escherichia coli in neonatal diarrhea of piglets was studied by comparing a K88-positive strain with three K88-negative strains derived from the K88-positive strain. K88 antigen was produced by the K88-positive strain in the intestinal tract of gnotobiotic piglets, whereas K88-negative strains did not regain the ability to synthesize K88 antigen. Synthesis of the antigen conferred different colonization characteristics on the four strains; K88-positive bacteria adhered to the mucosa of the small intestine, whereas K88-negative bacteria did not attach and were distributed throughout the lumen. Adhesion of K88-positive bacteria to tissue from the small intestine of gnotobiotic piglets was demonstrated in vitro and was inhibited by antisera that contained K88 antibodies. Attachment did not occur with bacteria grown at 18 C. Adhesion of cell-free K88 antigen was also demonstrated. The K88-positive strain and one of the K88-negative strains were equally virulent in gnotobiotic piglets. In contrast, the K88-positive strain killed 50% of conventionally reared piglets, whereas the K88-negative strain killed only 3%. Adhesion of the K88-positive strain, but not of the K88-negative strain, to the mucosa of the small intestine was demonstrated. Our results show that K88 antigen is responsible for attachment of K88-positive bacteria to the wall of the small intestine, and that adhesion is essential for the virulence of K88-positive bacteria in conventionally reared piglets. Neonatal diarrhea in piglets is characterized by the proliferation of certain strains of Escherichia coli in the small intestine (41). Colonization of the anterior small intestine by these strains followed by their multiplication to reach large numbers (41) and production of enterotoxins (21, 28, 39) results in clinical disease. The comparatively small numbers of non-enteropathogenic strains of E. coli in the small intestine of apparently healthy piglets (24, 41) may be due, in part, to the removal of bacteria by gut motility (1, 11, 18). Adhesion of E. coli to the intestinal epithelium has been demonstrated (2, 12, 13, 14, 40, 44, 46, 50), and it is possible that attachment allows enteropathogenic strains to overcome gut motility and to reach large numbers in the small intestine. Strains of enteropathogenic E. coli isolated from diseased piglets frequently possess K88 antigen (20, 45, 52). In contrast to the other K antigens, K88 is a protein component (48) that forms a substantial layer of fine filaments on the surface of the cell (47). Its synthesis is controlled by a plasmid that can be spontaneously lost (30). Ad

In vitro inhibition of adhesion of enterotoxigenic Escherichia coli K88 to piglet intestinal mucus by egg-yolk antibodies

“…Antigenic variants referred to as K88ab, -ac, and -ad ¢mbriae have been identi¢ed [2,3]. These ¢mbriae mediate the adhesion of E. coli K88 strains to the epithelial mucosa lining of the intestine [4] and thereby contribute to their virulence [5]. Inhibition of adhesion of E. coli K88 to the host at this stage may reduce the virulence of the pathogen.…”

On the relative importance of specific and non-specific approaches to oral microbial adhesion

“…E. coli strains can elaborate tip-localized proteins on pap fimbria¢, which are important in uroepithelial attachment [39]. K88 and K99 are other E. Table 1 coli fimbrial antigens which complex with receptors on intestinal epithelium [40,41]. Oral microorganisms also possess a wide variety, of specific adhesin molecules.…”

Current and Future Applications of Monoclonal Antibodies against Bacteria in Veterinary Medicine

“…The K88 antigen was first described in 1961 as a serologically distinct antigen associated with E. coli strains isolated from pigs with edema disease and neonatal enteritis (105). It was later demonstrated that the K88 antigen was an adherence factor which facilitated colonization of the small intestine (6,65,158). This was confirmed by several in vivo and in vitro studies wherein adherence of K88-positive EPEC to intestinal villous epithelium was blocked by antisera against the K88 antigen (65,134,138,158).…”

“…It was later demonstrated that the K88 antigen was an adherence factor which facilitated colonization of the small intestine (6,65,158). This was confirmed by several in vivo and in vitro studies wherein adherence of K88-positive EPEC to intestinal villous epithelium was blocked by antisera against the K88 antigen (65,134,138,158). Based on these findings, vaccine trials were carried out and demonstrated that sows vaccinated with K88-positive EPEC would produce high levels of colostral K88-specific antibody which would passively protect newborn suckling pigs from enteric disease produced by K88-positive EPEC (119,120).…”