Pseudomonas aeruginosaOspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection
Open Access
- 23 December 2009
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 75 (1), 76-91
- https://doi.org/10.1111/j.1365-2958.2009.06955.x
Abstract
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 H2O2 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 β‐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 H2O2 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 β‐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.Keywords
This publication has 57 references indexed in Scilit:
- Pseudomonas aeruginosa - Candida albicans Interactions: Localization and Fungal Toxicity of a Phenazine DerivativeApplied and Environmental Microbiology, 2009
- The role of quorum sensing in chronic cystic fibrosisPseudomonas aeruginosainfectionsFEMS Microbiology Letters, 2009
- A new oxidative sensing and regulation pathway mediated by the MgrA homologue SarZ in Staphylococcus aureusMolecular Microbiology, 2008
- The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanismProceedings of the National Academy of Sciences of the United States of America, 2008
- Conversion of Bacillus subtilis OhrR from a 1-Cys to a 2-Cys Peroxide SensorJournal of Bacteriology, 2008
- Redox-Active Antibiotics Control Gene Expression and Community Behavior in Divergent BacteriaScience, 2008
- Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosisMicrobiology, 2008
- Discovering mechanisms of signaling-mediated cysteine oxidationCurrent Opinion in Chemical Biology, 2008
- Bacillus anthracis -derived nitric oxide is essential for pathogen virulence and survival in macrophagesProceedings of the National Academy of Sciences of the United States of America, 2008
- Cytotoxicity of Pseudomonas Secreted Exotoxins Requires OxyR ExpressionJournal of Surgical Research, 2007