Identification of a lactate-quinone oxidoreductase (Lqo) in staphylococcus aureus that is essential for virulence
In: Frontiers in Cellular and Infection Microbiology, Jg. 1 (2011-12-01)
Online
academicJournal
Zugriff:
Staphylococcus aureus is an important human pathogen commonly infecting nearly every host tissue. The ability of S. aureus 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, S. aureus immediately excretes copious amounts of L-lactate to maintain redox balance. However, after prolonged NO·-exposure, S. aureus 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 (KM = ~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, ∆lqo 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-/-). We demonstrate that S. aureus NO·-resistance is highly dependent on the availability of a glycolytic carbon sources. However, S. aureus 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 S. aureus myocarditis. Thus, Lqo provides S. aureus with yet another means of replicating in the presence of host NO·.
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Identification of a lactate-quinone oxidoreductase (Lqo) in staphylococcus aureus that is essential for virulence
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Autor/in / Beteiligte Person: | James R Fuller ; Nicholas P Vitko ; Perkowski, Ellen F. ; eScott, Eric ; eKhatri, Dal ; Jeffrey S Spontak ; Lance R Thurlow ; Anthony R Richardson |
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Zeitschrift: | Frontiers in Cellular and Infection Microbiology, Jg. 1 (2011-12-01) |
Veröffentlichung: | Frontiers Media S.A., 2011 |
Medientyp: | academicJournal |
ISSN: | 2235-2988 (print) |
DOI: | 10.3389/fcimb.2011.00019 |
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