Flagella Co-expressed Colonization Determinants of Campylobacter jejuni

Campylobacter jejuni is a food-borne pathogen and one of the main causes of bacterial gastroenteritis in humans throughout the world.  This Gram-negative bacterium is also a commensal organism of the intestinal tracts of wild and agriculturally-significant birds and animals.  Flagellar motility is the only virulence and colonization factor proven to be required for infection of human volunteers to promote disease and it is also required for infection of chicks for commensalism.  Expression of some flagellar components such as the major flagellin and other filament genes requires an alternative sigma factor, σ²⁸.  Analysis of the σ²⁸ regulon revealed a subset of genes which are co-expressed with flagellar genes but are not required for motility.  In a natural chick model of infection, we discovered that some of these σ²⁸-dependent genes were required for wild-type levels of commensal colonization of the chick ceca, suggesting these factors are colonization determinants not involved in motility.  We annotated these genes Flagellar co-expressed colonization determinants (Feds).  Further characterization of these σ²⁸-dependent genes revealed that fedA is required for invasion of intestinal cells. Bioinformatic analyses indicate that FedA is a single-domain hemerythrin that binds iron and oxygen molecules.  We also discovered that a ΔfedA mutant has reduced aerotolerance when C. jejuni is exposed to atmospheric levels of oxygen, and that FedA is needed for survival under limited iron conditions.  Overall, we provide evidence that the flagellar system is a global regulatory system that coordinates production of flagella with colonization and virulence determinants to promote host interactions.