Role of respiratory NADH oxidation in the regulation of Staphylococcus aureus virulence

Lici A. Schurig-Briccio, Paola K. Parraga Solorzano, Andrea M. Lencina, Jana N. Radin, Grischa Y. Chen, John Demian Sauer, Thomas E. Kehl-Fie, Robert B. Gennis

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere45832
JournalEMBO Reports
Volume21
Issue number5
DOIs
StatePublished - May 6 2020

Keywords

  • NADH dehydrogenase
  • NADH/NAD
  • Staphylococcus aureus
  • respiratory chain
  • two-component system

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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