Alteration of genetic content and gene expression modulate the pathogenic potential of Campylobacter jejuni.

摘要

A leading cause of bacterial gastroenteritis worldwide, Campylobacter jejuni is responsible for as many as 2.5 million reported cases per year in the United States of America alone. Campylobacter is a flagellated, spiral shaped, Gram-negative bacterium. The development of new genetic tools and availability of the C. jejuni genome sequence has accelerated the progress made in the field of Campylobacter pathogenesis in the past decade. Although a number of virulence determinants have been identified, to date their role in the ability of Campylobacter to cause disease remains unknown. The research presented in this dissertation highlights two distinct features by which C. jejuni is able to "toggle" between a virulent and an avirulent state. First, C. jejuni is able to alter its genetic content to exhibit variable motility phenotype. It is proposed that alternating between a motile and a non-motile state helps Campylobacter switch from its commensal lifestyle in one host to an invasive lifestyle in the other. The data presented in Chapter 2 indicate that the differences observed in the virulence phenotype of two poultry isolates CS and S2B were a result of a point mutation in the flgR and rpoN genes, respectively. Proteins encoded by both these genes are essential for flagellar biosynthesis, thus mutations in these genes rendered the organism non-motile and hence avirulent. Second, Campylobacter alters its virulence potential by modulating its gene expression in response to an environmental stimulus. To adapt and survive within the intestinal tract Campylobacter must alter its genes expression in response to the varied in vivo conditions encountered including exposure to bile. The data presented in chapter three demonstrate that culture in the presence of bile salts enhances the virulence potential of Campylobacter. When cultured in the presence of the bile salt sodium deoxycholate, C. jejuni undergoes a synthetic response characterized by the upregulation of genes known to play a role in Campylobacter pathogenesis. Taken together, the data presented show that Campylobacter is able to vary its virulence potential by altering its genetic content and gene expression.