An Iron-Regulated Alkyl Hydroperoxide Reductase (AhpC) Confers Aerotolerance and Oxidative Stress Resistance to the Microaerophilic Pathogen Campylobacter jejuni

Abstract

ABSTRACTMicroaerophiles likeCampylobacter jejunimust resist oxidative stresses during transmission or infection. Growth ofC. jejuni81116 under iron limitation greatly increased the expression of two polypeptides of 26 and 55 kDa. The identification of these proteins by N-terminal amino acid sequencing showed both to be involved in the defense against oxidative stress. The 55-kDa polypeptide was identical toC. jejunicatalase (KatA), whereas the N terminus of the 26-kDa polypeptide was homologous to a 26-kDaHelicobacter pyloriprotein. The gene encoding theC. jejuni26-kDa protein was cloned, and the encoded protein showed significant homology to the small subunit of alkyl hydroperoxide reductase (AhpC). The upstream region ofahpCencoded a divergent ferredoxin (fdxA) homolog, whereas downstream sequences containedflhBandmotBhomologs, which are involved in flagellar motility. There was no evidence for an adjacent homolog ofahpF, encoding the large subunit of alkyl hydroperoxide reductase. Reporter gene studies showed that iron regulation ofahpCandkatAis achieved at the transcriptional level. Insertional mutagenesis of theahpCgene resulted in an increased sensitivity to oxidative stresses caused by cumene hydroperoxide and exposure to atmospheric oxygen, while resistance to hydrogen peroxide was not affected. TheC. jejuniAhpC protein is an important determinant of the ability of this microaerophilic pathogen to survive oxidative and aerobic stress.