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.
Richardson
Anthony R
AR
Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
Libby
Stephen J
SJ
Fang
Ferric C
FC
D000818:Animals; D004790:Enzyme Induction; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007113:Immunity, Innate; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence
D007527:Isoenzymes; D007773:Lactates; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; C409676:lactate dehydrogenase 2; C409667:lactate dehydrogenase 1; D005947:Glucose