The msaABCR Operon Regulates the Response to Oxidative Stress in Staphylococcus aureus

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Biological Sciences


Staphylococcus aureus has evolved a complex regulatory network that controls a multitude of defense mechanisms against the deleterious effects of oxidative stress stimuli subsequently leading to the pathogen's survival and persistence in the hosts. Previously, we characterized the msaABCR operon as a regulator of virulence, antibiotic resistance, and the formation of persister cells in S. aureus. Deletion of the msaABCR operon resulted in downregulation of several genes involved in resistance against oxidative stress. Notably, those include carotenoid biosynthetic genes and the osmC/ohr gene, which is involved in resistance against organic hydroperoxides. These findings led us to hypothesize that the msaABCR operon is involved in resisting oxidative stress generated in the presence of both H2O2 and organic hydroperoxides. Here we report that a protein product of the msaABCR operon (MsaB) transcriptionally regulates the expression of the crtOPQMN operon and the osmC/ohr gene to resist in vitro oxidative stresses. In addition to its direct regulation of the crtOPQMN operon and osmC/ohr gene, we also show that MsaB is the transcriptional repressor of sarZ (repressor of osmC/ohr).Taken together, these results suggest that the msaABCR operon regulates an oxidative-stress defense mechanism, which is required to facilitate persistent and recurrent staphylococcal infections. Moving forward, we plan to investigate the role of msaABCR in the persistence of S. aureus under in vivo conditions.

IMPORTANCE: This study shows the involvement of the msaABCR operon in resisting oxidative stress by S. aureus generated under in vitro and ex vivo conditions. We show that MsaB regulates the expression and production of a carotenoid pigment, staphyloxanthin, which is a potent antioxidant in S. aureus. We also demonstrate that MsaB regulates the osmC/ohr gene, which is involved in defending against oxidative stress generated by organic hydroperoxides. This study highlights the importance of msaABCR in the survival of S. aureus in the presence of various environmental stimuli that mainly exert oxidative stress. The findings from this study indicate the possibility that msaABCR is involved in the persistence of staphylococcal infections and therefore could be a potential antimicrobial target to overcome recalcitrant staphylococcal infections.

Publication Title

Journal of Bacteriology

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