Staphylococcus aureus is a gram-positive opportunistic pathogen responsible for a variety of chronic and acute infections. Continued emergence of S. aureus antimicrobial resistance has garnered this pathogen significant notoriety and a desperate need for new therapeutic interventions. While mobile genetic elements confer resistance to cell wall targeting antibiotics, the emergence of drug resistant small colony variants (SCVs) is also common during S. aureus infection. SCVs have specific mutations in central metabolic pathways (heme, thymidine, etc.) that render them drug resistant. We are actively engaged in exploring phenotypic and virulence traits of distinct SCV genotypes and the impacts of their presence in both the cystic fibrosis lung and chronic wound infections.