6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus
The drug efflux mechanism adopted by Staphylococcus aureus helps it in its survival under antibiotic pressure. The efflux pump NorA, a member of the MFS superfamily, effluxes out fluoroquinolones, biocides, quaternary ammonium compounds, and anti-infectives. Therefore, in a continuous effort to iden...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | The Microbe |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S295019462500130X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849316098790391808 |
|---|---|
| author | Shashikanta Sau Sarika Sharma Gopal L. Khatik Sandeep Sharma Nitin Pal Kalia |
| author_facet | Shashikanta Sau Sarika Sharma Gopal L. Khatik Sandeep Sharma Nitin Pal Kalia |
| author_sort | Shashikanta Sau |
| collection | DOAJ |
| description | The drug efflux mechanism adopted by Staphylococcus aureus helps it in its survival under antibiotic pressure. The efflux pump NorA, a member of the MFS superfamily, effluxes out fluoroquinolones, biocides, quaternary ammonium compounds, and anti-infectives. Therefore, in a continuous effort to identify new scaffolds as NorA inhibitors, we in the present study screened 6-gingerol ((5S)-5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl) decan-3-one) for its role as a NorA efflux pump inhibitor. 6-gingerol dramatically decreased the intracellular invasion and ciprofloxacin minimum inhibitory concentration (MIC) in NorA, overproducing S. aureus SA-1199B. Furthermore, 6-gingerol enhanced the killing efficacy and minimized the mutation frequency of ciprofloxacin. The accumulation of ethidium bromide, another substrate for NorA efflux pump, was significantly inhibited by 6-gingerol. A molecular docking on NorA protein suggested the potential role of 6-gingerol in inhibiting efflux pump via binding at the protein's active site. 6-gingerol showed an excellent binding affinity of −5.8 kcal/mol at NorA protein. Further, in an intracellular invasion assay performed using J774A. 1 macrophage cell lines, 6-gingerol significantly reduced the invasion of S. aureus SA-1199B (NorA overproducing) by 2 Log10. For the first time, the study delineated the role of 6-gingerol as an efflux pump inhibitor of S. aureus with a significant impact on intracellular invasion of the bacteria. |
| format | Article |
| id | doaj-art-e6564e3ad93341198a069558d65e008b |
| institution | Kabale University |
| issn | 2950-1946 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Microbe |
| spelling | doaj-art-e6564e3ad93341198a069558d65e008b2025-08-20T03:51:58ZengElsevierThe Microbe2950-19462025-06-01710036210.1016/j.microb.2025.1003626-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureusShashikanta Sau0Sarika Sharma1Gopal L. Khatik2Sandeep Sharma3Nitin Pal Kalia4Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500037, IndiaDepartment of Sponsored Research, Lovely Professional University, Phagwara, Punjab 144411, IndiaDepartment of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, NIPER, Raebareli, Uttar Pradesh 226002, IndiaDepartment of Medical Laboratory Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; Corresponding authors.Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500037, India; Corresponding authors.The drug efflux mechanism adopted by Staphylococcus aureus helps it in its survival under antibiotic pressure. The efflux pump NorA, a member of the MFS superfamily, effluxes out fluoroquinolones, biocides, quaternary ammonium compounds, and anti-infectives. Therefore, in a continuous effort to identify new scaffolds as NorA inhibitors, we in the present study screened 6-gingerol ((5S)-5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl) decan-3-one) for its role as a NorA efflux pump inhibitor. 6-gingerol dramatically decreased the intracellular invasion and ciprofloxacin minimum inhibitory concentration (MIC) in NorA, overproducing S. aureus SA-1199B. Furthermore, 6-gingerol enhanced the killing efficacy and minimized the mutation frequency of ciprofloxacin. The accumulation of ethidium bromide, another substrate for NorA efflux pump, was significantly inhibited by 6-gingerol. A molecular docking on NorA protein suggested the potential role of 6-gingerol in inhibiting efflux pump via binding at the protein's active site. 6-gingerol showed an excellent binding affinity of −5.8 kcal/mol at NorA protein. Further, in an intracellular invasion assay performed using J774A. 1 macrophage cell lines, 6-gingerol significantly reduced the invasion of S. aureus SA-1199B (NorA overproducing) by 2 Log10. For the first time, the study delineated the role of 6-gingerol as an efflux pump inhibitor of S. aureus with a significant impact on intracellular invasion of the bacteria.http://www.sciencedirect.com/science/article/pii/S295019462500130XMulti drug resistanceStaphylococcus aureusDrug effluxNosocomial infectionsEfflux pump inhibitors |
| spellingShingle | Shashikanta Sau Sarika Sharma Gopal L. Khatik Sandeep Sharma Nitin Pal Kalia 6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus The Microbe Multi drug resistance Staphylococcus aureus Drug efflux Nosocomial infections Efflux pump inhibitors |
| title | 6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus |
| title_full | 6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus |
| title_fullStr | 6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus |
| title_full_unstemmed | 6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus |
| title_short | 6-gingerol enhances ciprofloxacin efficacy by inhibiting NorA efflux pump in Staphylococcus aureus |
| title_sort | 6 gingerol enhances ciprofloxacin efficacy by inhibiting nora efflux pump in staphylococcus aureus |
| topic | Multi drug resistance Staphylococcus aureus Drug efflux Nosocomial infections Efflux pump inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S295019462500130X |
| work_keys_str_mv | AT shashikantasau 6gingerolenhancesciprofloxacinefficacybyinhibitingnoraeffluxpumpinstaphylococcusaureus AT sarikasharma 6gingerolenhancesciprofloxacinefficacybyinhibitingnoraeffluxpumpinstaphylococcusaureus AT gopallkhatik 6gingerolenhancesciprofloxacinefficacybyinhibitingnoraeffluxpumpinstaphylococcusaureus AT sandeepsharma 6gingerolenhancesciprofloxacinefficacybyinhibitingnoraeffluxpumpinstaphylococcusaureus AT nitinpalkalia 6gingerolenhancesciprofloxacinefficacybyinhibitingnoraeffluxpumpinstaphylococcusaureus |