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.