Identification of a lactate-quinone oxidoreductase in Staphylococcus aureus that is essential for virulence.
Identification of a lactate-quinone oxidoreductase in Staphylococcus aureus that is essential for virulence.
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DOI：
10.3389/fcimb.2011.00019
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发表时间：
2011
影响因子：
5.7
通讯作者：
Richardson AR
中科院分区：
文献类型：
--
作者：
Fuller JR;Vitko NP;Perkowski EF;Scott E;Khatri D;Spontak JS;Thurlow LR;Richardson AR
金黄色葡萄球菌是一种重要的人类病原体，通常感染几乎所有宿主组织。金黄色葡萄球菌抵抗先天免疫的能力对其作为病原体的成功至关重要，包括其在宿主一氧化氮 (NO·) 存在的情况下生长的倾向。接触外源性NO·后，金黄色葡萄球菌立即分泌大量L-乳酸以维持氧化还原平衡。然而，在长时间暴露于 NO·-之后，金黄色葡萄球菌会特异性地重新同化 L-乳酸，在这项工作中，我们将负责这种 L-乳酸消耗的酶确定为 L-乳酸醌氧化还原酶 (Lqo, SACOL2623)。最初注释为 Mqo2，被认为可以氧化苹果酸，我们发现这种酶对苹果酸没有亲和力，但与 L-乳酸发生特异性反应 (KM = ∼330 μM)。除了在NO·胁迫期间需要重新同化L-乳酸之外，Lqo对于以L-乳酸作为唯一碳源的呼吸生长也至关重要。此外，Δlqo突变体在脓毒症小鼠模型中表现出减弱，特别是其引起心肌炎的能力。有趣的是，这种心脏特异性的衰减在无法合成炎性NO·（iNOS−/−）的小鼠中被完全消除。我们证明金黄色葡萄球菌的NO·抗性高度依赖于糖酵解碳源的可用性。然而，在NO·胁迫期间，金黄色葡萄球菌可以以Lqo依赖性方式利用肽和L-乳酸的组合作为碳源。与肾或肝组织相比，小鼠心脏组织具有显着高水平的L-乳酸，这与金黄色葡萄球菌心肌炎中对Lqo的NO·依赖性需求一致。因此，Lqo为金黄色葡萄球菌提供了在宿主NO·存在下进行复制的另一种方式。
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, Δlqo 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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影响因子：
3.2
作者：
STOCKLAND, AE;SANCLEME.CL
通讯作者：
SANCLEME.CL
影响因子：
4.4
作者：
Thurlow, Lance R.;Hanke, Mark L.;Kielian, Tammy
通讯作者：
Kielian, Tammy
影响因子：
0.7
作者：
Sakharov, D. A.;Shkurnikov, M. U.;Tonevitsky, A. G.
通讯作者：
Tonevitsky, A. G.
DOI：
10.1099/00221287-78-1-83
发表时间：
1973-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
STEVENSON, PM;HOLDSWORTH, ES
通讯作者：
HOLDSWORTH, ES
DOI：
10.2741/1021
发表时间：
2003-05-01
期刊：
FRONTIERS IN BIOSCIENCE
影响因子：
--
作者：
Wasi, F;Shuter, J
通讯作者：
Shuter, J