Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection |
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Authors: | Lefu Lan Thomas S Murray Barbara I Kazmierczak Chuan He |
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Institution: | Department of Chemistry, 929 East 57th Street, The University of Chicago, Chicago, IL 60637, USA.; Department of Pediatrics and Laboratory Medicine and;Department of Internal Medicine and Microbial Pathogenesis, Yale University, 333 Cedar St., New Haven, CT 06520, USA. |
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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 ( o xidative s tress response and p igment production R egulator) 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. |
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