Identification of Campylobacter jejuni Genes Involved in the Response to Acidic pH and Stomach Transit

Abstract

Campylobacter jejuni causes food-and waterborne gastroenteritis, and as such it must survive passage through the stomach in order to reach the gastrointestinal tract. While little is known about how C. jejuni survives transit through the stomach, its low infectious dose suggests it is well equipped to sense and respond to acid shock. In this study, the transcriptional profile of C. jejuni NCTC 11168 was obtained after the organism was exposed to in vitro and in vivo (piglet stomach) acid shock. The observed down-regulation of genes encoding ribosomal proteins likely reflects the need to reshuffle energy toward the expression of components required for survival. Acid shock also caused C. jejuni to up-regulate genes involved in stress responses. These included heat shock genes as well as genes involved in the response to oxidative and nitrosative stress. A role for the chaperone clpB in acid resistance was confirmed in vitro. Some genes showed expression patterns that were markedly different in vivo and in vitro, which likely reflects the complexity of the in vivo environment. For instance, transit through the stomach was characterized by up-regulation of genes that encode products that are involved in the use of nitrite as a terminal electron acceptor and down-regulation of genes that are involved in capsular polysaccharide expression. In conclusion, this study has enabled us to understand how C. jejuni modulates gene expression in response to acid shock in vitro and to correlate this with gene expression profiles of C. jejuni as it transits through the host stomach.

Identification of Campylobacter jejuni Genes Contributing to Acid Adaptation by Transcriptional Profiling and Genome-Wide Mutagenesis

“…This observation suggests that the expression of the PerR protein is posttranscriptionally controlled and/or that the PerR protein is deactivated under acidic conditions and thus is unable to repress the PerR-regulated genes. Interestingly, the perR gene also was highly up-regulated in response to both in vitro and in vivo acid shock (71), further suggesting that the modulation of PerR levels is a general response to acid stress in C. jejuni. While there are no previous reports implicating PerR in bacterial acid stress responses, its homologue, the ferric uptake regulator Fur, is required for the induction of acid shock genes and proteins in H. pylori and S. enterica (30,32,36), and the mutation of fur in these bacteria renders cells acid sensitive (4,6,8,10,30,36).…”

“…The C. jejuni genome encodes an additional ppk homologue, the expression of which was not affected under steady-state acid stress conditions. In fact, the ppk gene (Cj1359) was up-regulated in response to both in vitro and in vivo acid shock in C. jejuni (71), supporting a role for polyphosphate accumulation in the acid stress response of this bacterium. Phosphate uptake genes also were up-regulated under acid shock conditions (pH 4) in Shewanella oneidensis (47).…”

“…The expression of cgb and other members of the nitrosative stress regulon is controlled by NssR (26). Under conditions of acid shock, the gene encoding a truncated hemoglobin (Cj0465c) was highly upregulated in C. jejuni (71). While this gene was implicated in mediating O 2 flux in Campylobacter (88) rather than being directly involved in detoxification, it is nonetheless a member of the NssR regulon (26).…”

“…In order to gain a more comprehensive picture of the acid stress response of C. jejuni, we merged the transcriptional profiles obtained after the growth of C. jejuni under acidic conditions with those obtained after exposure to acid shock (pH 4.5) in vitro (71). Genes differentially expressed in response to growth at pH 6.5, 6.0, and/or 5.5 were included in our analysis.…”

“…In a complementary study, we identified genes for which expression was affected in response to acid shock (71). Here, we strive to understand how C. jejuni modulates gene expression to allow adaptation to growth under mildly acidic pH conditions.…”