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Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection.
Lan, Lefu; Murray, Thomas S; Kazmierczak, Barbara I; He, Chuan.
Afiliação
  • Lan L; Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Mol Microbiol ; 75(1): 76-91, 2010 Jan.
Article em En | MEDLINE | ID: mdl-19943895
Oxidative stress is one of the main challenges bacteria must cope with during infection. Here, we identify a new oxidative stress sensing and response ospR (oxidative stress response and pigment production Regulator) gene in Pseudomonas aeruginosa. Deletion of ospR leads to a significant induction in H(2)O(2) resistance. This effect is mediated by de-repression of PA2826, which lies immediately upstream of ospR and encodes a glutathione peroxidase. Constitutive expression of ospR alters pigment production and beta-lactam resistance in P. aeruginosa via a PA2826-independent manner. We further discovered that OspR regulates additional genes involved in quorum sensing and tyrosine metabolism. These regulatory effects are redox-mediated as addition of H(2)O(2) or cumene hydroperoxide leads to the dissociation of OspR from promoter DNA. A conserved Cys residue, Cys-24, plays the major role of oxidative stress sensing in OspR. The serine substitution mutant of Cys-24 is less susceptible to oxidation in vitro and exhibits altered pigmentation and beta-lactam resistance. Lastly, we show that an ospR null mutant strain displays a greater capacity for dissemination than wild-type MPAO1 strain in a murine model of acute pneumonia. Thus, OspR is a global regulator that senses oxidative stress and regulates multiple pathways to enhance the survival of P. aeruginosa inside host.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Proteínas Repressoras / Estresse Fisiológico / Regulação Bacteriana da Expressão Gênica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Microbiol Assunto da revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Proteínas Repressoras / Estresse Fisiológico / Regulação Bacteriana da Expressão Gênica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Microbiol Assunto da revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Estados Unidos