A phase-variable mechanism controlling the Campylobacter jejuni FlgR response regulator influences commensalism

Phase variation of genes in bacteria enables phenotypic alteration to modulate interactions within a host as conditions change. To promote commensalism in animals and disease in humans, Campylobacter jejuni produces a flagellar organelle for motility. In addition to tight transcriptional regulation of flagellar genes, C. jejuni also controls flagellar biosynthesis by phase variation. In this study, an unusual phase-variable mechanism controlling production of FlgR, the response regulator of the FlgSR two-component system required for transcription of σ⁵⁴-dependent flagellar genes, is identified. Phase variation of FlgR production is due to loss or gain of a nucleotide in homopolymeric adenine or thymine tracts within flgR. This mechanism occurs during commensalism in poultry to alter the colonization capacity of C. jejuni, presumably by influencing the motility phenotype of the bacterium. These findings provide more understanding into the genetic and colonization strategies C. jejuni employs to achieve commensalism in a natural host. Second, due to the richness of the C. jejuni genome in adenine or thymine residues and the apparent lack of the normal set of mismatch repair enzymes, the results from this study may suggest that the C. jejuni genome is more unstable and variable than previously realized. Furthermore, phase variation of flagellar motility by targeting flgR may be a phenomenon specific to C. jejuni that is absent in other Campylobacter species and contribute to reasons why C. jejuni is more frequently found as a commensal organism in poultry and as the cause of disease in humans.