
The author argues that the agr quorum-sensing system in S. aureus provides protection against lethal oxidative stress by controlling endogenous ROS levels, thereby enhancing resilience to exogenous ROS attacks.


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The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus . We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and fermentation but decreased ATP levels and growth, suggesting that Δ agr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δ agr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA , which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δ agr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived “memory” of agr -mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2−/−) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

### Competing Interest Statement

B.S. has consulted for Basilea Pharmaceutica. V.J.T. has received honoraria from Pfizer and MedImmune, and is an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc. provides research funding and other payments associated with a licensing agreement. All other authors: no competing interests declared.

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress

Quorum-sensing-agr-system-of-Staphylococcus-aureus-and-Protection-from-Lethal-Oxidative-Stress


Quorum-sensing agr system of Staphylococcus aureus and Protection from Lethal Oxidative Stress
