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AirSR, a [2Fe-2S] Cluster-Containing Two-Component System, Mediates Global Oxygen Sensing and Redox Signaling in Staphylococcus aureus
- Sun, Fei, Ji, Quanjiang, Jones, Marcus B., Deng, Xin, Liang, Haihua, Frank, Bryan, Telser, Joshua, Peterson, Scott
N., Bae, Taeok, He, Chuan
- Journal of the American Chemical Society 2012 v.134 no.1 pp. 305-314
- Staphylococcus aureus, anaerobic conditions, ciprofloxacin, cysteine, genes, host-pathogen relationships, hydrogen peroxide, microbial physiology, mutagenesis, mutants, nitric oxide, norfloxacin, oxidation, oxygen, phosphorylation, superoxide anion, transcriptomics, vancomycin
- Oxygen sensing and redox signaling significantly affect bacterial physiology and host-pathogen interaction. Here we show that a Staphylococcus aureus two-component system, AirSR (anaerobic iron-sulfur cluster-containing redox sensor regulator, formerly YhcSR), responds to oxidation signals (O₂, H₂O₂, NO, etc) by using a redox-active [2Fe-2S] cluster in the sensor kinase AirS. Mutagenesis studies demonstrate that the [2Fe-2S] cluster is essential for the kinase activity of AirS. We have also discovered that a homologue of IscS (SA1450) in S. aureus is active as a cysteine desulfurase, which enables the in vitro reconstitution of the [2Fe-2S] cluster in AirS. Phosphorylation assays show that the oxidized AirS with a [2Fe-2S]²⁺ cluster is the fully active form of the kinase but not the apo-AirS nor the reduced AirS possessing a [2Fe-2S]⁺ cluster. Overoxidation by prolonged exposure to O₂ or contact with H₂O₂ or NO led to inactivation of AirS. Transcriptome analysis revealed that mutation of airR impacts the expression of ∼355 genes under anaerobic conditions. Moreover, the mutant strain displayed increased resistance toward H₂O₂, vancomycin, norfloxacin, and ciprofloxacin under anaerobic conditions. Together, our results show that S. aureus AirSR is a redox-dependent global regulatory system that plays important roles in gene regulation using a redox active Fe–S cluster under O₂-limited conditions.