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

PLoS Pathogens

Sarah Dubrac¹  Tarek Msadek¹  Olivier Poupel¹  Isabelle Martin-Verstraete²  Olga Soutourina² 

[1] Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, CNRS URA 2172, Paris, France;Institut Pasteur, Unité de Génétique des Génomes Bactériens, CNRS URA 2171, Paris, France

关键词: Staphylococcus aureus;    Cysteine;    Regulator genes;    Oxidative stress;    Gene expression;    Macrophages;    Nitrites;    Gene regulation;   

DOI  :  10.1371/journal.ppat.1000894

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 ΔcymR 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 ΔcymR 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 ΔcymR 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.

【 授权许可】

CC BY