Culture of Campylobacter jejuni with Sodium Deoxycholate Induces Virulence Gene Expression

Abstract

Campylobacter jejuni, a spiral-shaped gram-negative bacterium, is a leading bacterial cause of human food-borne illness. Acute disease is associated with C. jejuni invasion of the intestinal epithelium. Further, maximal host cell invasion requires the secretion of proteins termed Campylobacter invasion antigens (Cia). As bile acids are known to alter the pathogenic behavior of other gastrointestinal pathogens, we hypothesized that the virulence potential of Campylobacter may be triggered by the bile acid deoxycholate (DOC). In support of this hypothesis, culturing C. jejuni with a physiologically relevant concentration of DOC significantly altered the kinetics of cell invasion, as shown by gentamicin protection assays. In contrast to C. jejuni harvested from Mueller-Hinton (MH) agar plates, C. jejuni harvested from MH agar plates supplemented with DOC secreted the Cia proteins, as judged by metabolic labeling experiments. DOC was also found to induce the expression of the ciaB gene, as determined by ␤-galactosidase reporter, real-time reverse transcription-PCR, and microarray analyses. Microarray analysis further revealed that DOC induced the expression of virulence genes (ciaB, cmeABC, dccR, and tlyA). In summary, we demonstrated that it is possible to enhance the pathogenic behavior of C. jejuni by modifying the culture conditions. These results provide a foundation for identifying genes expressed by C. jejuni in response to in vivo-like culture conditions.

Bile Salts Induce Resistance to Polymyxin in Enterohemorrhagic Escherichia coliO157:H7

“…Bile has also been demonstrated to be an environmental signal that controls the expression of colonization and virulence factors of several enteric bacteria (13,27,28,31,36,50,51,54,55,65). Much of the work on Gram-negative bacteria's response to bile has been performed with Salmonella (9, 44, 51-54, 57, 59, 68).…”

Identification and Characterization of an Invasion Antigen B Gene from the Oral Pathogen Campylobacter rectus

“…Among the best studied virulence factors of campylobacters is the invasion antigen gene B (ciaB) of C. jejuni, which has been shown to play a key role in host cell invasion [18][19][20]. In C. jejuni, CiaB has been shown to be a secreted protein, although it lacks a predictable signal peptide [19].…”

“…Among the best studied C. jejuni virulence factors is the ciaB gene, which has been shown to play a critical role in host cell invasion; and therefore pathogenesis [18][19][20]. In addition, ciaB genes have been identified from additional campylobacters including Campylobacter lari, Campylobacter coli, and Campylobacter upsaliensis [21,22].…”

Calcium Enhances Bile Salt-Dependent Virulence Activation in Vibrio cholerae

“…Many pathogenic bacteria have also adapted to integrate exposure to bile acids into their virulence regulation mechanisms. In Campylobacter jejuni, many virulence genes are positively regulated by bile (49). Deoxycholate specifically promotes the expression of major virulence factors, including invasion antigens, leading to more rapid invasion of epithelial cells.…”