| Summary: | <p>Abstract</p> <p>Background</p> <p>During gut colonization, the enteric pathogen <it>Campylobacter jejuni </it>must surmount the toxic effects of reactive oxygen species produced by its own metabolism, the host immune system, and intestinal microflora. Elucidation of <it>C. jejuni </it>oxidative stress defense mechanisms is critical for understanding <it>Campylobacter </it>pathophysiology.</p> <p>Results</p> <p>The mechanisms of oxidative stress defense in <it>C. jejuni </it>were characterized by transcriptional profiling and phenotypic analysis of wild-type and mutant strains. To define the regulon of the peroxide-sensing regulator, PerR, we constructed an isogenic Δ<it>perR </it>mutant and compared its transcriptome profile with that of the wild-type strain. Transcriptome profiling identified 104 genes that belonged to the PerR regulon. PerR appears to regulate gene expression in a manner that both depends on and is independent of the presence of iron and/or H<sub>2</sub>O<sub>2</sub>. Mutation of <it>perR </it>significantly reduced motility. A phenotypic analysis using the chick colonization model showed that the Δ<it>perR </it>mutant exhibited attenuated colonization behavior. An analysis of changes in the transcriptome induced by exposure to H<sub>2</sub>O<sub>2</sub>, cumene hydroperoxide, or menadione revealed differential expression of genes belonging to a variety of biological pathways, including classical oxidative stress defense systems, heat shock response, DNA repair and metabolism, fatty acid biosynthesis, and multidrug efflux pumps. Mutagenic and phenotypic studies of the superoxide dismutase SodB, the alkyl-hydroxyperoxidase AhpC, and the catalase KatA, revealed a role for these proteins in oxidative stress defense and chick gut colonization.</p> <p>Conclusion</p> <p>This study reveals an interplay between PerR, Fur, iron metabolism and oxidative stress defense, and highlights the role of these elements in <it>C. jejuni </it>colonization of the chick cecum and/or subsequent survival.</p>
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