The success of Staphylococcus aureus as a pathogen is due to its capability of fine-tuning its cellular physiology to meet the challenges presented by diverse environments, which allows it to colonize multiple niches within a single vertebrate host. Elucidating the roles of energy-yielding metabolic pathways could uncover attractive therapeutic strategies and targets. In this work, we seek to determine the effects of disabling NADH-dependent aerobic respiration on the physiology of S. aureus. Differing from many pathogens, S. aureus has two type-2 respiratory NADH dehydrogenases (NDH-2s) but lacks the respiratory ion-pumping NDHs. Here, we show that the NDH-2s, individually or together, are not essential either for respiration or growth. Nevertheless, their absence eliminates biofilm formation, production of α-toxin, and reduces the ability to colonize specific organs in a mouse model of systemic infection. Moreover, we demonstrate that the reason behind these phenotypes is the alteration of the fatty acid metabolism. Importantly, the SaeRS two-component system, which responds to fatty acids regulation, is responsible for the link between NADH-dependent respiration and virulence in S. aureus.

中文翻译：

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呼吸NADH氧化在金黄色葡萄球菌毒力调节中的作用。

金黄色葡萄球菌作为病原体的成功归因于其微调其细胞生理学能力以应对各种环境所带来的挑战的能力，这使其能够在单个脊椎动物宿主内定殖多个壁ni。阐明产生能量的代谢途径的作用可以发现有吸引力的治疗策略和靶标。在这项工作中，我们试图确定禁用NADH依赖的有氧呼吸对金黄色葡萄球菌生理的影响。与许多病原体不同，金黄色葡萄球菌具有两种2型呼吸NADH脱氢酶（NDH-2s），但缺乏呼吸离子泵NDH。在这里，我们表明NDH-2s单独或一起对于呼吸或生长不是必需的。然而，它们的缺失消除了生物膜的形成，α-毒素的产生，并降低了在全身性感染小鼠模型中定植特定器官的能力。此外，我们证明了这些表型背后的原因是脂肪酸代谢的改变。重要的是，响应脂肪酸调节的SaeRS两组分系统负责NADH依赖的呼吸作用与金黄色葡萄球菌的毒力之间的联系。