Repurposing Approved Drugs as Fluoroquinolone Potentiators to Overcome Efflux Pump Resistance in Staphylococcus aureus
Nisha Mahey, Rushikesh Tambat, Nishtha Chandal, Dipesh Kumar Verma, Krishan Gopal Thakur, Hemraj Nandanwar
Abstract
-based screening of FDA-approved drugs that identified six different molecules able to inhibit NorA pump (Major Facilitator Superfamily). Our study highlights that these compounds bind to and block the activity of the NorA pump and increase the sensitivity of S. aureus and methicillin-resistant S. aureus to fluoroquinolones. These drugs combined with fluoroquinolones significantly reduced the preformed biofilms and displayed significant efficacy in the murine thigh infection model when compared to untreated control and ciprofloxacin alone.
Topics & Concepts
EffluxStaphylococcus aureusCiprofloxacinPotentiatorPharmacologyMicrobiologyAntibioticsMedicineNorfloxacinMinimum inhibitory concentrationNalidixic acidChemistryOfloxacinMethicillin-resistant Staphylococcus aureusAntibiotic resistanceAntibacterial agentBacteriaStaphylococcal infectionsDrug resistancePathogenMultiple drug resistanceDNA gyrasePseudomonas aeruginosaLinezolidDrugEthidium bromideAntibiotic Resistance in BacteriaNosocomial Infections in ICUAntimicrobial Resistance in Staphylococcus