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Our lab is focused on understanding the adaptive changes in S. aureus that take place during infection. An integrated approach is used that incorporates new technologies to detect low abundance variants in pooled bacterial populations, traditional bacterial and evolutionary genetics, and molecular population genetic analysis. A special focus of these studies is on the identification of within-host variation in the agr locus, a global regulator of virulence in S. aureus. agr mutants are attenuated for virulence in animal models of infection, and the majority of clinical isolates have a functional agr locus. However, agr-defective strains are frequently recovered from patients with a variety of hospital-acquired infections, suggesting that the occurrence of these strains may be favored under certain in vivo conditions. This work is motivated by practical questions in infectious diseases (such as the best use of antimicrobials that target agr and virulence), as well as more basic yet closely intertwined questions, such as how to explain the alterations that are responsible for adaptive changes at different stages of S. aureus infections.