PUBLICATION

NAD kinase promotes Staphylococcus aureus pathogenesis by supporting production of virulence factors and protective enzymes

Authors
Leseigneur, C., Boucontet, L., Duchateau, M., Pizarro-Cerda, J., Matondo, M., Colucci-Guyon, E., Dussurget, O.
ID
ZDB-PUB-220622-59
Date
2022
Source
eLIFE   11: (Journal)
Registered Authors
Boucontet, Laurent, Colucci-Guyon, Emma
Keywords
AgrA, NADK, infection, infectious disease, macrophage, microbiology, staphylococcus, virulence, zebrafish
MeSH Terms
  • Animals
  • NAD/metabolism
  • NADP/metabolism
  • Phosphotransferases (Alcohol Group Acceptor)/metabolism
  • Staphylococcus aureus*/genetics
  • Staphylococcus aureus*/metabolism
  • Virulence Factors*/genetics
  • Zebrafish/metabolism
PubMed
35723663 Full text @ Elife
Abstract
Nicotinamide adenine dinucleotide phosphate (NADPH) is the primary electron donor for reductive reactions that are essential for the biosynthesis of major cell components in all organisms. Nicotinamide adenine dinucleotide kinase (NADK) is the only enzyme that catalyzes the synthesis of NADP(H) from NAD(H). While the enzymatic properties and physiological functions of NADK have been thoroughly studied, the role of NADK in bacterial pathogenesis remains unknown. Here, we used CRISPR interference to knock down NADK gene expression to address the role of this enzyme in Staphylococcus aureus pathogenic potential. We find that NADK inhibition drastically decreases mortality of zebrafish infected with S. aureus. Furthermore, we show that NADK promotes S. aureus survival in infected macrophages by protecting bacteria from antimicrobial defense mechanisms. Proteome-wide data analysis revealed that production of major virulence-associated factors is sustained by NADK. We demonstrate that NADK is required for expression of the quorum-sensing response regulator AgrA, which controls critical S. aureus virulence determinants. These findings support a key role for NADK in bacteria survival within innate immune cells and the host during infection.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping