TY - JOUR
T1 - Role of respiratory NADH oxidation in the regulation of Staphylococcus aureus virulence
AU - Schurig-Briccio, Lici A.
AU - Parraga Solorzano, Paola K.
AU - Lencina, Andrea M.
AU - Radin, Jana N.
AU - Chen, Grischa Y.
AU - Sauer, John Demian
AU - Kehl-Fie, Thomas E.
AU - Gennis, Robert B.
N1 - We thank members of the Gennis laboratory for their help and useful discussions. We thank Dr. C. Rock for sharing his valuable insights and helpful discussions, and providing the plasmids pCS1191 and pJ507. We also thank Drs. J. Boyd for kindly providing the strains JMB2047 and JMB2057, C. Lee the strains CYL1171 and CYL1171, and A. Richardson the wild-type strains LAC and UAMS-1. This work was supported by operating grants for the National Institutes of Health to RBG (R01 GM095600 and R01 HL16101), TEKF (K22 AI104805 and R01 AI118880), and JDS (R01 CA188034), a Basil O'Connor Starter Scholar Award from March of Dimes to TEKF. Strains NE1801 and NE1884 were obtained through Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) for distribution by BEI Resources, NIAID, NIH: Nebraska Transposon Mutant Library (NTML) Screening Array.
We thank members of the Gennis laboratory for their help and useful discussions. We thank Dr. C. Rock for sharing his valuable insights and helpful discussions, and providing the plasmids pCS1191 and pJ507. We also thank Drs. J. Boyd for kindly providing the strains JMB2047 and JMB2057, C. Lee the strains CYL1171 and CYL1171, and A. Richardson the wild‐type strains LAC and UAMS‐1. This work was supported by operating grants for the National Institutes of Health to RBG (R01 GM095600 and R01 HL16101), TEKF (K22 AI104805 and R01 AI118880), and JDS (R01 CA188034), a Basil O'Connor Starter Scholar Award from March of Dimes to TEKF. Strains NE1801 and NE1884 were obtained through Network on Antimicrobial Resistance in (NARSA) for distribution by BEI Resources, NIAID, NIH: Nebraska Transposon Mutant Library (NTML) Screening Array. Staphylococcus aureus
PY - 2020/5/6
Y1 - 2020/5/6
N2 - 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.
AB - 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.
KW - NADH dehydrogenase
KW - NADH/NAD
KW - Staphylococcus aureus
KW - respiratory chain
KW - two-component system
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UR - http://www.scopus.com/inward/citedby.url?scp=85082134196&partnerID=8YFLogxK
U2 - 10.15252/embr.201845832
DO - 10.15252/embr.201845832
M3 - Article
C2 - 32202364
AN - SCOPUS:85082134196
SN - 1469-221X
VL - 21
JO - EMBO Reports
JF - EMBO Reports
IS - 5
M1 - e45832
ER -