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Inhibition of Staphylococcus aureus PriA Helicase by Flavonol Kaempferol

Yen-Hua Huang1, Chien-Chih Huang, Cheng-Chieh Chen

  • 1School of Biomedical Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung City, Taiwan.

The Protein Journal
|April 21, 2015
PubMed

Insights

Flavonols kaempferol and myricetin inhibit Staphylococcus aureus PriA (SaPriA), an essential enzyme for bacterial survival. This discovery offers potential new strategies for combating healthcare-associated infections caused by S. aureus.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Staphylococcus aureus is a significant cause of healthcare-associated infections.
  • Bacterial helicases, like S. aureus PriA (SaPriA), are crucial for DNA replication restart and bacterial survival.
  • Identifying novel inhibitors of essential bacterial enzymes is vital for developing new antimicrobial strategies.

Purpose of the Study:

  • To investigate the inhibitory effects of flavonoids on Staphylococcus aureus PriA (SaPriA).
  • To explore the potential of natural products as therapeutic agents against S. aureus.

Main Methods:

  • Vanadate-sensitive colorimetric assay to measure ATP hydrolysis by SaPriA.
  • Enzyme inhibition assays to determine IC50 values.
  • Fluorescence quenching to assess the binding kinetics of flavonoids to SaPriA.

Main Results:

  • Kaempferol and myricetin significantly inhibited SaPriA activity at 35 μM, reducing phosphate concentration by 37% and 69%, respectively.
  • The IC50 of kaempferol for SaPriA was determined to be 22 ± 2 μM.
  • Kaempferol demonstrated binding to SaPriA with a K(d) of 9.1 ± 3.2 μM.

Conclusions:

  • Flavonols, specifically kaempferol and myricetin, are potent inhibitors of Staphylococcus aureus PriA.
  • These findings represent the first report of natural products targeting the SaPriA helicase.
  • This study highlights the potential of kaempferol and myricetin as leads for developing novel anti-staphylococcal agents.

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