Abstract
BackgroundDuring 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.ResultsThe 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 ΔperR 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 ΔperR 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.ConclusionThis 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.
Highlights
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
We have described the transcriptional response of C. jejuni to H2O2, cumene hydroperoxide, and menadione exposure
Our results revealed that oxidants have a broad impact on genes involved in a variety of biological pathways, from classical oxidative stress defense systems and iron metabolism, to multidrug efflux pumps, heat shock proteins, DNA repair and metabolism, fatty acid biosynthesis, and membrane structure biogenesis
Summary
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. Campylobacter infection is an acute diarrheal disease with symptoms that range from a day of mild watery or bloody diarrhea to severe abdominal pain that can last for several weeks [1]. This pathogen has been implicated in the development of Guillain-Barré syndrome and is a suspected eti-. During the course of normal metabolism, C. jejuni will unavoidably be exposed to reactive oxygen species (ROS) [6] These ROS, which include superoxide radicals (O2·-), hydrogen peroxide (H2O2) and hydroxyl radicals (·OH), are formed by the stepwise one-electron reduction of molecular oxygen [6]. Microorganisms have developed specialized and inducible defense mechanisms to protect against oxidative stress [13]
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