title: AirSR, a [2Fe-2S] cluster-containing two-component system, mediates global oxygen sensing and redox signaling in Staphylococcus aureus.
abstract: 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 (O(2), H(2)O(2), 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 O(2) or contact with H(2)O(2) 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 H(2)O(2), 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 O(2)-limited conditions.
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, USA.
authors: Fei
authors: F
authors: Sun
authors: Quanjiang
authors: Q
authors: Ji
authors: Marcus B
authors: MB
authors: Jones
authors: Xin
authors: X
authors: Deng
authors: Haihua
authors: H
authors: Liang
authors: Bryan
authors: B
authors: Frank
authors: Joshua
authors: J
authors: Telser
authors: Scott N
authors: SN
authors: Peterson
authors: Taeok
authors: T
authors: Bae
authors: Chuan
authors: C
authors: He
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004777:Environment; D006861:Hydrogen Peroxide / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D013057:Spectrum Analysis; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D007506:Iron-Sulfur Proteins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D010100:Oxygen