ArticleScientific reports2024
Thymoquinone' potent impairment of multidrug-resistant Staphylococcus aureus NorA efflux pump activity.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Lupeol as a modulator of bacterial resistance mediated by the MepA efflux pump in Staphylococcus aureus.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- From Natural Product to Topical Antimicrobial Candidate: EvaluatingPharmaceuticals (Basel, Switzerland) · 2026Article
- Dual antibacterial and pro-healing effects of thymoquinone in an experimental infected diabetic wound model.BMC complementary medicine and therapies · 2026Article
- Exploring the Multifaceted Phytochemical Profile ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Novel plasmid curing mediated restoration of antimicrobial sensitivity by Nigella sativa extract against multidrug resistant Staphylococcus aureus.Scientific reports · 2026Article
- Screening ofFrontiers in microbiology · 2026Article
- Thymoquinone combined with conventional antibiotics against pandrug-resistantFrontiers in pharmacology · 2026Article
- Characterization and Antimicrobial Resistance Profiles of Biofilm Forming Strains ofMicroorganisms · 2025Article
- Thymoquinone/β-Frontiers in cellular and infection microbiology · 2025Article
- Efflux pumps: gatekeepers of antibiotic resistance inMicrobial cell (Graz, Austria) · 2024Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The drug efflux pump is a crucial mechanism implicated in resistance to multiple antimicrobials. Thymoquinone (TQ) has evidently demonstrated multiple activities, antibacterial being the most effective. Knowledge about TQ activity against multidrug-resistant Staphylococcus aureus is very scarce. Therefore, the present study was conducted to investigate TQ resistance modulation in ciprofloxacin (CIP) and doxycycline (DO) multidrug-resistant S. aureus. Forty-seven samples were collected from different sources, and S. aureus was isolated and identified. Then, S. aureus resistance profiles to antimicrobials, N. sativa essential oil, and TQ; the correlation between TQ-MIC readings and disc diffusion; cartwheel and ethidium bromide (EtBr) accumulation assays; and norA gene expression were all described within silico molecular docking for TQ interactions with norA efflux pump protein. TQ-MICs ranged from 5-320 µg/ml. TQ down-regulated norA gene expression, resulting in a drop in efflux pump activity of 77.5-90.6% in the examined strains, comparable to that observed with verapamil. Exposure of S. aureus strains to CIP and DO raises the initial basal efflux pumping expression to 34.2 and 22.9 times, respectively. This induced efflux pumping overexpression was substantially reduced by 97.7% when TQ was combined with CIP or DO. There was a significant reduction of MICs of CIP and DO MICs by 2-15 and 2-4 folds, respectively, after treatment with 0.5XMIC-TQ in resistance modulation assays. These results refer to TQ ligand inhibitory interactions with NorA protein in molecular docking. Interpretations of inhibition zone diameters (IZDs) of disc diffusion and TQ-MICs exhibit independence of MICs from IZDs, as indicated by invalid linear regression analysis. TQ significantly reduced efflux pumping S. aureus induced by CIP and DO, but further investigations are needed to improve TQ-pharmacokinetics to restore CIP and DO activity and suppress fluoroquinolone and doxycycline-resistant S. aureus selection in clinical and animal settings.
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