Evaluation of phyto-gallic acid as a potential inhibitor of Staphylococcus aureus efflux pump mediated tetracycline resistance: an in-vitro and in-silico study

Abstract

Plants contain many bioactive compounds with potent antibacterial and efflux pump inhibitory activity (EPI). In this study, gallic acid extracted from pomegranate molasses by analytical HPLC holds promise as an EPI drug for Staphylococcus aureus mediated tetracycline resistance, it lowered the bacterial resistance and reversed the mechanism via tet family efflux pump, using molecular technique and in-silico molecular docking analysis. Extracted gallic acid combined with tetracycline demonstrated a significant decrease in the minimal inhibitory concentration MIC compared to its single activity. Similarly, little growth and lower fluorescence of S. aureus were observed on ethidium bromide (2.5 mg/mL) agar plates, indicating a reversible efflux pump mechanism and a potent EPI activity. Molecular docking demonstrated a promising affinity binding energy between gallic acid and tet efflux genes, opening a new baseline in bacterial infection treatment. PCR for tetK and Qac A/B genes failed to show any relation between tet genes and gallic acid.

Graphical Abstract

Keywords:

• Efflux pump inhibitor
• phyto-constituent
• gallic acid
• tet genes
• cartwheel method
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

NM: Conceiving the idea, performing the experiments, writing the first draft, editing the manuscript; RA: Performing the HPLC analysis, GS: Editing the manuscript, SG: Molecular docking analysis; SA: Formal analysis; AS: Editing the manuscript. All authors read and agreed on the final draft.

Data availability statement

Data are available upon request from the corresponding author.

Additional information

Funding

This project was supported by Researchers Supporting Project Number (RSP2024R216), King Saud University, Riyadh, Saudi Arabia.