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
