title: Characterization of the oxidative stress stimulon and PerR regulon of Campylobacter jejuni.
abstract: BACKGROUND
  During gut colonization, the enteric pathogen Campylobacter jejuni must surmount the toxic effects of reactive oxygen species produced by its own metabolism, the host immune system, and intestinal microflora. Elucidation of C. jejuni oxidative stress defense mechanisms is critical for understanding Campylobacter pathophysiology.
  
  
  RESULTS
  The mechanisms of oxidative stress defense in C. jejuni 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 DeltaperR 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 H2O2. Mutation of perR significantly reduced motility. A phenotypic analysis using the chick colonization model showed that the DeltaperR mutant exhibited attenuated colonization behavior. An analysis of changes in the transcriptome induced by exposure to H2O2, 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.
  
  
  CONCLUSIONS
  This study reveals an interplay between PerR, Fur, iron metabolism and oxidative stress defense, and highlights the role of these elements in C. jejuni colonization of the chick cecum and/or subsequent survival.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA. Kiran.Palyada@mpiresearch.com
authors.forename: Kiran
authors.initials: K
authors.lastname: Palyada
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Sun
authors.forename: Annika
authors.initials: A
authors.lastname: Flint
authors.forename: James
authors.initials: J
authors.lastname: Butcher
authors.forename: Hemant
authors.initials: H
authors.lastname: Naikare
authors.forename: Alain
authors.initials: A
authors.lastname: Stintzi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001555:Benzene Derivatives / Q000494:pharmacology; D016123:Campylobacter jejuni / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002432:Cecum / Q000382:microbiology; D002645:Chickens / Q000382:microbiology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D012329:RNA, Bacterial / Q000235:genetics; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D001555:Benzene Derivatives; D012329:RNA, Bacterial; D012097:Repressor Proteins; C122138:peroxide repressor proteins; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D007501:Iron; C007164:cumene hydroperoxide