期刊
EMBO REPORTS
卷 21, 期 5, 页码 -出版社
WILEY
DOI: 10.15252/embr.201845832
关键词
NADH dehydrogenase; NADH; NAD(+); respiratory chain; Staphylococcus aureus; two-component system
资金
- National Institutes of Health [R01 GM095600, R01 HL16101, K22 AI104805, R01 AI118880, R01 CA188034]
- Basil O'Connor Starter Scholar Award from March of Dimes
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 alpha-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.
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