title: Pseudomonas aeruginosa OspR is an oxidative stress sensing regulator that affects pigment production, antibiotic resistance and dissemination during infection.
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 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.
authors: Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
authors: Lefu
authors: L
authors: Lan
authors: Thomas S
authors: TS
authors: Murray
authors: Barbara I
authors: BI
authors: Kazmierczak
authors: Chuan
authors: C
authors: He
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress; D010860:Pigments, Biological / Q000096:biosynthesis; D011014:Pneumonia / Q000382:microbiology; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological; D014443:Tyrosine / Q000378:metabolism; D014774:Virulence; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010860:Pigments, Biological; D012097:Repressor Proteins; D047090:beta-Lactams; D014443:Tyrosine; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase