Abstract
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.
Highlights
Cysteine, an important sulfur-containing amino acid, plays a major role in cellular physiology
Upregulation of genes involved in oxidative stress response and metal ion homeostasis in the DcymR mutant
A more detailed analysis of these transcriptome data, carried out by hierarchical clustering, showed derepression of directly CymR-dependent sulfur metabolic genes in the DcymR mutant [25], and revealed increased expression of genes involved in detoxification processes such as oxidative stress response and metal ion homeostasis
Summary
An important sulfur-containing amino acid, plays a major role in cellular physiology. Links between bacterial virulence and cysteine metabolism have been described. Cysteine-containing molecules such as thioredoxin and glutathione play an important role in protecting cells against oxidative stress [10,11]. Several studies have shown that cysteine itself plays a role in bacterial sensitivity to oxidative stress [15,16,17,18,19,20,21]. Recent data report the existence of links between cysteine metabolism and the response to various stressors such as hydrogen peroxide, superoxide, diamide, nitric oxide, thiol-reactive electrophiles and metal ions [18,20,22,23,24]
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