Oxidative stress drives the selection of quorum sensing mutants in the Staphylococcus aureus population

Significance The QS Agr system of the pathogen S. aureus is a social trait based on bacterial population density that orchestrates the expression of toxins crucial for virulence. Paradoxically, Agr-defective mutants are selected during infection. We studied the selection and fitness of agr mutants under infection-relevant conditions, such as antibiotic stress and hypoxia. Under aerobic growth, the Agr-controlled PSM toxins are produced. These are toxic for Staphylococci and select for agr mutants, which are nonproducers. Contrastingly, hypoxia favors QS maintenance and even allows hyperactivation of the system without imposing a fitness burden. We propose that changing oxygen environments encountered during infection not only alters the virulence potential, but also the course of microbial evolution of the S. aureus community.