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The quorum-sensing agr system protects Staphylococcus aureus from oxidative stress (5 hour growth)

ABSTRACT: The agr quorum-sensing system clearly links Staphylococcus aureus metabolism to virulence, but little is known about how agr alters metabolism to affect cell survival during severe stress. Recently, we reported that agr activity increases survival of bacteria during treatment with lethal concentrations of H2O2, a crucial host defense against S. aureus. Here we report that protection by agr extends to growth resumption during the exit from stationary phase. The data indicate that the agr functionality of a cell’s ancestor affects stress-resiliency after resuming growth. Protection against killing by H2O2 depended on the agr effector molecule RNAIII and Rot, a transcription factor targeted by RNAIII. Expression data revealed that Δagr strains shift to fermentation, suggesting that agr promotes aerobic respiration. Epistasis between mutation of agr and sortase, which anchors surface proteins to the cell wall, suggested that reduced killing by H2O2 of wild-type agr strains acts through down-regulation of surface proteins that perturb respiration. Respiration generates reactive oxygen species (ROS), moderate amounts of which can protect from subsequent challenge by lethal concentrations, explaining agr-mediated protection against subsequent lethal H2O2 doses. Increased survival of wild-type agr cells in response to H2O2 required sodA, which dismutates O2- to H2O2, suggesting that sodA helps induce the low, protective levels of ROS triggered by agr. Additionally, detrimental effects of the Δagr mutation require ahpC, which functions to decrease the intracellular level of H2O2. Deletion of ahpC or sortase attenuated neutrophil-mediated killing of Δagr strains, demonstrating the importance of priming in anticipation of impending immune attack.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE206889 | GEO | 2023/06/20

REPOSITORIES: GEO

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The quorum-sensing agr system protects Staphylococcus aureus from oxidative stress (5 hour growth)

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