POTENTIATION OF CIPROFLOXACIN ACTIVITY BY CHALCONES BY MODULATING EFFLUX PUMP AND BIOFILM REGULATORY GENE IN STAPHYLOCOCCUS AUREUS

BHAWANDEEP KAUR; SHASHIKANTA SAU; SUMAN K. JANA; NITIN PAL KALIA; GOPAL LAL KATHIK; ASHISH SUTTEE; SARIKA SHARMA; SANDEEP SHARMA

doi:10.22159/ijap.2025v17i4.54253

Authors

BHAWANDEEP KAUR Department of Medical Laboratory Sciences, School of Allied Medical Sciences Lovely Professional University Phagwara (Punjab), India https://orcid.org/0000-0002-4401-4522
SHASHIKANTA SAU Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research. Hyderabad, India https://orcid.org/0000-0003-3728-5110
SUMAN K. JANA Department of Medical Laboratory Sciences, School of Allied Medical Sciences Lovely Professional University Phagwara (Punjab), India https://orcid.org/0009-0009-7784-9612
NITIN PAL KALIA Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research. Hyderabad, India
GOPAL LAL KATHIK Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Raebareli, India
ASHISH SUTTEE Department of Pharmacognosy, Lovely Professional University, India https://orcid.org/0000-0003-3539-281X
SARIKA SHARMA Department of Sponsored Research, Lovely Professional University, India
SANDEEP SHARMA Department of Medical Laboratory Sciences, School of Allied Medical Sciences Lovely Professional University Phagwara (Punjab), India https://orcid.org/0000-0001-9172-8512

DOI:

https://doi.org/10.22159/ijap.2025v17i4.54253

Keywords:

Chalcones, Efflux pump inhibition, Biofilm inhibition, Antibiotic resistance, Agr gene expression, S. aureus

Abstract

Objective: Natural and synthetic compounds with dual activity to inhibit efflux pumps and biofilm production in Staphylococcus aureus (S. aureus) were investigated in this study. Chalcones emerged as potential compounds with the possibility to inhibit efflux pump and biofilm production at once.

Methods: We performed pre-clinical screenings of different chalcones-ciprofloxacin combinations with a NorA overexpressing S. aureus strain. Chalcones inhibition of the NorA

efflux pump and Agr gene expression, a major regulator of biofilm formation, were tested. In silico modeling was also used to confirm the dual inhibitory activity of chalcones.

Results: Chalcones effectively modulated the action of ciprofloxacin by reducing the MIC by 2-8 fold and improving the time kill study, also inhibiting the NorA efflux pump and suppressing Agr gene expression, resulting in increased antibacterial activity and decreased biofilm formation.

Conclusion: The present research brings to the limelight chalcones as dual-function inhibitors aiming at efflux-based antibiotic resistance and biofilm formation in S. aureus with a potential strategy to repress drug-resistant infections.

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