Identification and analysis of flagellar coexpressed determinants (Feds) of Campylobacter jejuni involved in colonization

Abstract

Summary The flagellum of Campylobacter jejuni provides motility essential for commensal colonization of the intestinal tract of avian species and infection of humans resulting in diarrhoeal disease. Additionally, the flagellar type III secretion system has been reported to secrete proteins such as CiaI that influence invasion of human intestinal cells and possibly pathogenesis. The flagellar regulatory system ultimately influences σ28 activity required for expression of the FlaA major flagellin and other flagellar filament proteins. In this work, we discovered that transcription of ciaI and four genes we propose annotating as feds (for flagellar coexpressed determinants) is dependent upon σ28, but these genes are not required for motility. Instead, the Feds and CiaI are involved in commensal colonization of chicks, with FedA additionally involved in promoting invasion of human intestinal cells. We also discovered that the major flagellin influences production, stability or secretion of σ28‐dependent proteins. Specific transcriptional and translational mechanisms affecting CiaI were identified and domains of CiaI were analysed for importance in commensalism or invasion. Our work broadens the genes controlled by the flagellar regulatory system and implicates this system in co‐ordinating production of colonization and virulence determinants with flagella, which together are required for optimal interactions with diverse hosts.

High-Throughput Sequencing of Campylobacter jejuni Insertion Mutant Libraries Reveals mapA as a Fitness Factor for Chicken Colonization

“…Of the 130 mutations with relative abundances of at least 0.01, 37 are in genes annotated as hypothetical proteins, though some hypothetical determinants have been shown to encode colonization factors. These include Cjj81176_0083 and Cjj81176_0414, which encode a new class of flagellar coexpressed determinants (Feds) required for full colonization of the chicken gastrointestinal tract (25). Thus, approximately 28% of those genes identified as required for colonization of the chicken gastrointestinal tract exhibit no significant primary homology to known protein domains, signaling that an immense amount of information still remains to be uncovered about C. jejuni colonization factors.…”

The Second Messenger Cyclic Di-GMP Regulates Clostridium difficile Toxin Production by Controlling Expression of sigD

“…A precedent for the regulation of genes unrelated to motility and chemotaxis by SigD homologues exists for several bacterial species (93)(94)(95)(96)(97). For example, in the diarrheal pathogen Vibrio cholerae, the SigD orthologue FliA similarly augments the production of cholera toxin (98).…”

A capsule conjugate vaccine approach to prevent diarrheal disease caused byCampylobacter jejuni

“…Flagella are critical to virulence for the organism to swim through the mucus lining of the intestine and to serve as a secretory organelle for a variety of proteins, some of which appear to play roles in invasion. [23][24][25][26][27] C. jejuni invasion is similar to that of Shigella spp., in that both usually invade the intestinal epithelium and are not generally found systemically, in contrast to Salmonella spp. The process of invasion of epithelial cells results in an influx of immune cells and cytokine release that is manifest as inflammatory diarrhea.…”