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Science 21 March 2008:
Vol. 319. no. 5870, pp. 1672 - 1676
DOI: 10.1126/science.1155207
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Reports

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 (NObullet) produced by activated phagocytes. We show that S. aureus is capable of metabolically adapting to nitrosative stress by expressing an NObullet-inducible L-lactate dehydrogenase (ldh1, SACOL0222) divergently transcribed from the NObullet-detoxifying flavohemoglobin (hmp). L-Lactate production allows S. aureus to maintain redox homeostasis during nitrosative stress and is essential for virulence. NObullet-inducible lactate dehydrogenase activity and NObullet 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

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Construction and Characterization of Three Lactate Dehydrogenase-Negative Enterococcus faecalis V583 Mutants.
M. Jonsson, Z. Saleihan, I. F. Nes, and H. Holo (2009)
Appl. Envir. Microbiol. 75, 4901-4903
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Science. ISSN 0036-8075 (print), 1095-9203 (online)