title: OxyR tightly regulates catalase expression in Neisseria meningitidis through both repression and activation mechanisms.
abstract: Mechanisms for coping with oxidative stress (OS) are crucial for the survival of pathogenic Neisseria spp. in the human host. In this study we investigate the mechanism by which OxyR finely regulates the catalase gene (kat) in Neisseria meningitidis. Detailed transcriptional analyses show that catalase is transcribed from a single promoter that is induced by H(2)O(2) in an OxyR-dependent manner and two key cysteine residues are essential for this. OxyR also represses the kat promoter: kat expression in the null mutant is at a constitutive intermediary level higher than uninduced, but lower than H(2)O(2)-induced levels in the wild type. Our data are consistent with a model in which OxyR binds to the kat promoter and exerts: (i) repression of transcription in the absence of OS signal and (ii) activation of the promoter in response to OS signal. This direct double-edged mechanism may ensure tight regulatory control of kat expression ensuring catalase is synthesized only when needed. In addition, our results provide an explanation for the altered OS resistance phenotypes seen in Neisseria mutant strains where, paradoxically, the oxyR mutants are more resistant than the wild type in oxidative killing assays.
authors.affiliation: Department of Microbial Molecular Biology, Novartis Vaccines, Siena, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ieva
authors.forename: Davide
authors.initials: D
authors.lastname: Roncarati
authors.forename: Matteo M E
authors.initials: MM
authors.lastname: Metruccio
authors.forename: Kate L
authors.initials: KL
authors.lastname: Seib
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scarlato
authors.forename: Isabel
authors.initials: I
authors.lastname: Delany
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050296:Microbial Viability; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009345:Neisseria meningitidis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D018384:Oxidative Stress; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012329:RNA, Bacterial / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D012097:Repressor Proteins; D006861:Hydrogen Peroxide; D002374:Catalase