A Nitric Oxide–Inducible Lactate Dehydrogenase Enables Staphylococcus aureus to Resist Innate Immunity

Staphylococcus aureus is one of the most successful human pathogens, colonizing 2 billion individuals worldwide and causing invasive infections even in immunocompetent hosts. S. aureus can evade multiple components of host innate immunity, including the antimicrobial radical nitric oxide (NO) produced by activated phagocytes. We show that S. aureus is capable of metabolically adapting to nitrosative stress by expressing an NO-inducible L-lactate dehydrogenase (ldh1, SACOL0222) divergently transcribed from the NO-detoxifying flavohemoglobin (hmp). L-Lactate production allows S. aureus to maintain redox homeostasis during nitrosative stress and is essential for virulence. NO-inducible lactate dehydrogenase activity and NO resistance distinguish S. aureus from the closely related commensal species S. epidermidis and S. saprophyticus.