Mucus colonization as a determinant of pathogenicity in intestinal infection by Campylobacter jejuni: a mouse cecal model

Abstract

Human isolates of the intestinal pathogen Campylobacter jejuni have been shown to colonize mucus on the outer surface and deep within the intestinal crypts of gnotobiotic or germfree mice. The cecal crypts are preferentially colonized. A model of mucus colonization by C. jejuni in the mouse cecum has been developed, using antibiotic- and magnesium sulfate-treated specific-pathogen-free animals. These spiral-shaped bacteria colonize the mucus in a similar manner to the normal spiral-shaped microbiota. No evidence of adhesion to the intestinal surface was found with a wide variety of microscopic techniques. The campylobacters were seen to be highly motile in living preparations of gut tissue and rapidly tracked along intestinal mucus. Just as many of the normal spiral-shaped bacteria of intestinal surfaces can achieve close association with the epithelium through mucus association and do not adhere to the surface, C. jejuni colonizes the intestinal mucosa via mucus colonization. Thus, a major determinant of pathogenicity in intestinal infection with C. jejuni is proposed to be an ability to colonize intestinal mucus. The possession of specific adhesins is unlikely to be a significant determinant of pathogenicity. Better understanding of the mechanism of mucus association and the properties of the bacterium that are responsible will provide a basis for the rational selection of preventative measures. The model of mucus association in adult antibiotic-treated mice provides an opportunity for colonization studies with variant organisms and immunization studies.