Using a combined metabolomics and transcriptomics approach, a new study reports that Staphylococcus aureus is highly dependent on de novo methionine biosynthesis to efficiently colonize the human nose. Accordingly, growth of S. aureus in a synthetic medium that mimicked the nasal environment was dependent on the methionine biosynthesis enzyme cysteine-γ-synthase (MetI), and metI mutants showed a decreased ability to colonize the noses of cotton rats. S. aureus colonization of the human nose is a major risk factor for invasive infections, but the authors report that a MetI inhibitor blocks bacterial growth, which suggests that this biosynthetic pathway could be a new antibacterial target.