AUTHOR=Fuller James R., Vitko Nicholas P., Perkowski Ellen F., Scott Eric , Khatri Dal , Spontak Jeffrey S., Thurlow Lance R., Richardson Anthony R.

TITLE=Identification of a Lactate-Quinone Oxidoreductase in Staphylococcus aureus that is Essential for Virulence

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=1

YEAR=2011

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2011.00019

DOI=10.3389/fcimb.2011.00019

ISSN=2235-2988

ABSTRACT=<p><italic>Staphylococcus aureus</italic> is an important human pathogen commonly infecting nearly every host tissue. The ability of <italic>S. aureus</italic> to resist innate immunity is critical to its success as a pathogen, including its propensity to grow in the presence of host nitric oxide (NO·). Upon exogenous NO· exposure, <italic>S. aureus</italic> immediately excretes copious amounts of L-lactate to maintain redox balance. However, after prolonged NO·-exposure, <italic>S. aureus</italic> reassimilates L-lactate specifically and in this work, we identify the enzyme responsible for this L-lactate-consumption as a L-lactate-quinone oxidoreductase (Lqo, SACOL2623). Originally annotated as Mqo2 and thought to oxidize malate, we show that this enzyme exhibits no affinity for malate but reacts specifically with L-lactate (<italic>K</italic><sub>M</sub> = ∼330 μM). In addition to its requirement for reassimilation of L-lactate during NO·-stress, Lqo is also critical to respiratory growth on L-lactate as a sole carbon source. Moreover, Δ<italic>lqo</italic> mutants exhibit attenuation in a murine model of sepsis, particularly in their ability to cause myocarditis. Interestingly, this cardiac-specific attenuation is completely abrogated in mice unable to synthesize inflammatory NO· (iNOS<sup>−/−</sup>). We demonstrate that <italic>S. aureus</italic> NO·-resistance is highly dependent on the availability of a glycolytic carbon sources. However, <italic>S. aureus</italic> can utilize the combination of peptides and L-lactate as carbon sources during NO·-stress in an Lqo-dependent fashion. Murine cardiac tissue has markedly high levels of L-lactate in comparison to renal or hepatic tissue consistent with the NO·-dependent requirement for Lqo in <italic>S. aureus</italic> myocarditis. Thus, Lqo provides <italic>S. aureus</italic> with yet another means of replicating in the presence of host NO·.</p>