Department of Biochemistry, University of Illinois, Urbana, IL, USA.
Department of Microbiology, University of Illinois, Urbana, IL, USA.
EMBO Rep. 2020 May 6;21(5):e45832. doi: 10.15252/embr.201845832. Epub 2020 Mar 23.
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.
金黄色葡萄球菌之所以能成为病原体，是因为它能够精细地调整细胞生理机能，以应对不同环境带来的挑战，从而使其能够在单一脊椎动物宿主的多个小生境中定植。阐明产能代谢途径的作用可能会揭示出有吸引力的治疗策略和靶点。在这项工作中，我们试图确定抑制 NADH 依赖的需氧呼吸对金黄色葡萄球菌生理机能的影响。与许多病原体不同，金黄色葡萄球菌有两种类型 2 的 NADH 脱氢酶（NDH-2s），但缺乏呼吸离子泵 NDHs。在这里，我们表明，NDH-2s 单独或一起对于呼吸或生长既不是必需的。然而，它们的缺失消除了生物膜的形成、α-毒素的产生，并降低了在系统性感染的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的原因是脂肪酸代谢的改变。重要的是，对脂肪酸调节做出响应的 SaeRS 双组分系统是金黄色葡萄球菌中 NADH 依赖的呼吸与毒力之间联系的关键。
