The Helical Shape of Campylobacter jejuni Promotes In Vivo Pathogenesis by Aiding Transit through Intestinal Mucus and Colonization of Crypts.

Abstract

Campylobacter jejuni is a helix-shaped enteric bacterial pathogen and a common cause of gastroenteritis. We recently developed a mouse model for this human pathogen utilizing the SIGIRR-deficient mouse strain, which exhibits significant intestinal inflammation in response to intestinal C. jejuni infection. In the current study, this mouse model was used to define whether C. jejuni's characteristic helical shape plays a role in its ability to colonize and elicit inflammation in the mouse intestine. Mice were infected with the previously characterized straight-rod Δpgp1 and Δpgp2 mutant strains, along with a newly characterized curved-rod Δ1228 mutant strain. We also compared the resultant infections and pathology to those elicited by the helix-shaped wild-type C. jejuni and complemented strains. Despite displaying wild-type colonization of the intestinal lumen, the straight-rod Δpgp1 and Δpgp2 mutants were essentially nonpathogenic, while all strains with a curved or helical shape retained their expected virulence. Furthermore, analysis of C. jejuni localization within the ceca of infected mice determined that the primary difference between the rod-shaped, nonpathogenic mutants and the helix-shaped, pathogenic strains was the ability to colonize intestinal crypts. Rod-shaped mutants appeared unable to colonize intestinal crypts due to an inability to pass through the intestinal mucus layer to directly contact the epithelium. Together, these results support a critical role for C. jejuni's helical morphology in enabling it to traverse and colonize the mucus-filled intestinal crypts of their host, a necessary step required to trigger intestinal inflammation in response to C. jejuni.