A Nitric Oxide–Inducible Lactate Dehydrogenase Enables Staphylococcus aureus to Resist Innate Immunity
Anthony R. Richardson,1
Stephen J. Libby,1
Ferric C. Fang1,2*
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.
1 Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
2 Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
* To whom correspondence should be addressed. E-mail: fcfang{at}u.washington.edu
