Diclofenac Sodium Inhibits the Gene Expression of the norB Efflux Pump in Clinical Methicillin-Resistant Staphylococcus aureus

Abstract

Background. Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health challenge because of its ability to resist multiple antibiotics, primarily through efflux pump mechanisms and the expression of resistance genes. Recent studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, may play a role in modulating bacterial resistance mechanisms.Aim. To investigate the impact of diclofenac sodium (Olfen) on the expression of the efflux pump gene norB in MRSA isolates and evaluate its potential for enhancing antibiotic efficacy.Methods. A total of 125 clinical samples were collected and analyzed for the presence of Staphylococcus aureus via phenotypic and molecular identification methods. Antibiotic susceptibility was assessed via the Kirby–Bauer disk diffusion method, whereas the minimum inhibitory concentration (MIC) was determined via the resazurin-based microplate dilution assay. The expression of efflux pump genes was quantified before and after diclofenac sodium treatment via quantitative real-time PCR (RT‒qPCR) and normalized to that of the housekeeping gene 16SrRNA.Results. PCR analysis confirmed the presence of the norB gene in 77% of the MRSA isolates. RT‒qPCR analysis demonstrated significant downregulation of norB expression following diclofenac sodium treatment. These findings suggest that diclofenac sodium may interfere with efflux pump activity, potentially restoring bacterial susceptibility to antibiotics.Conclusion. These findings indicate that diclofenac sodium can modulate efflux pump gene expression in MRSA, reducing bacterial resistance mechanisms. This study highlights the potential of NSAIDs as adjunctive agents for combating antibiotic-resistant infections.