The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

• DOI: 10.1371/journal.ppat.1000894
• Publication Date: 2010-05-13T20:04:34Z
• Authors: Olga Soutourina; Sarah Dubrac; Olivier Poupel; Tarek Msadek; Isabelle Martin-V...
• Keywords: [SDV]Life Sciences [q-bio]; MESH: Virulence; Mice; MESH: Oxidants; MESH: Staphylococcus aureus; MESH: Up-Regulation; Homeostasis; MESH: Animals; Disulfides; Biology (General); Mice, Inbred BALB C; 0303 health sciences; MESH: Oxidative Stress; Virulence; Staphylococcal Infections; Oxidants; Up-Regulation; 3. Good health; MESH: Copper; [SDV] Life Sciences [q-bio]; MESH: Tellurium; MESH: Homeostasis; MESH: Hydrogen Peroxide; Cystine; Female; MESH: Genes, Bacterial; Tellurium; Research Article; Staphylococcus aureus; QH301-705.5; MESH: Mice, Inbred BALB C; MESH: Staphylococcal Infections; Cell Line; 03 medical and health sciences; [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology; Animals; MESH: Disulfides; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; MESH: Mice; Macrophages; MESH: Macrophages; MESH: Cystine; Hydrogen Peroxide; RC581-607; MESH: Cell Line; Oxidative Stress; MESH: Gene Deletion; Genes, Bacterial; Immunologic diseases. Allergy; MESH: Female; Copper; Gene Deletion

We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a DeltacymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the DeltacymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the DeltacymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host.