A new oxidative sensing and regulation pathway mediated by the MgrA homologue SarZ in Staphylococcus aureus

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Abstract
Summary: Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses from the human pathogen Staphylococcus aureus. Among these, a thiol‐based oxidation sensing pathway through a global regulator MgrA controls the virulence and antibiotic resistance of the bacterium. Herein, we report a new thiol‐based oxidation sensing and regulation system that is mediated through a parallel global regulator SarZ. SarZ is a functional homologue of MgrA and is shown to affect the expression of ∼87 genes in S. aureus. It uses a key Cys residue, Cys‐13, to sense oxidative stress and to co‐ordinate the expression of genes involved in metabolic switching, antibiotic resistance, peroxide stress defence, virulence, and cell wall properties. The discovery of this SarZ‐mediated regulation, mostly independent from the MgrA‐based regulation, fills a missing gap of oxidation sensing and response in S. aureus.