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Cirsiliol and Quercetin Inhibit ATP Synthesis and Decrease the Energy Balance in Methicillin-Resistant Staphylococcus

Silvia Ravera1, Gabriele Tancreda1, Luigi Vezzulli2

  • 1Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.

Molecules (Basel, Switzerland)
|September 9, 2023
PubMed

Insights

Two flavones, cirsiliol and quercetin, effectively inhibit bacterial ATP synthase, reducing intracellular ATP levels in antibiotic-resistant strains. These compounds show potential as novel antibacterial agents targeting essential energy production pathways.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Antibiotic resistance poses a significant global health threat.
  • Polyphenols exhibit antibacterial properties and target bacterial energy production.
  • F1Fo-ATP synthase is crucial for bacterial homeostasis and a potential drug target.

Purpose of the Study:

  • To evaluate the impact of flavones cirsiliol and quercetin on ATP synthase activity and intracellular ATP levels in MRSA and MRSE.
  • To compare the efficacy of these flavones with oligomycin, a known ATP synthase inhibitor.
  • To assess the potential of cirsiliol and quercetin as adjuncts to conventional antibiotics.

Main Methods:

  • Real-time quantitative ATP synthesis assays using luminometry.
  • Measurement of total intracellular ATP content in permeabilized Gram-positive bacteria.
  • Treatment of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) strains with cirsiliol, quercetin, and oligomycin.

Main Results:

  • Cirsiliol and quercetin significantly inhibited ATP synthase and reduced intracellular ATP levels in both MRSA and MRSE strains.
  • The inhibitory effect was more pronounced in the MRSE strain.
  • Cirsiliol and quercetin demonstrated immediate inhibitory action, unlike oligomycin which showed a delayed effect.

Conclusions:

  • Cirsiliol and quercetin effectively target bacterial ATP synthase, leading to decreased intracellular ATP.
  • These flavones represent promising candidates for novel antibacterial strategies, potentially overcoming resistance mechanisms.
  • Their ability to inhibit ATP synthase offers a unique mechanism of action against antibiotic-resistant bacteria.
Keywords:
ATP synthesisF1Fo-ATP synthasecirsiliolflavonoidsmethicillin-resistant Staphylococcus aureus (MRSA)methicillin-resistant Staphylococcus epidermidis (MRSE)oligomycinquercetin

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