FDA-approved drugs for targeting virulence of Pseudomonas aeruginosa: A drug repurposing approach to combat multidrug resistance.

The rise of multidrug-resistant (MDR) Pseudomonas aeruginosa remains an unresolved and substantial challenge to public health, which highlights an urgent need for newer therapeutic strategies. Despite the availability of innumerable antibiotics that effectively eliminate bacterial infections, their unregulated consumption and overexploitation has promoted the development of multidrug resistance by inducing selection pressure. As the world progresses into the post-antibiotic era, antivirulence therapies that exploit a 'disarm-don't kill approach' are gaining momentum as a promising alternative to existing antimicrobial regimens. In view of extensive research being conducted to explore alternate intervention strategies against P. aeruginosa, this review augments scientific literature on repurposing of Food and Drug Administration (FDA)-approved drugs as antivirulence agents, focusing on their ability to disarm quorum sensing (QS), suppress virulence factor production, and disrupt biofilm formation. Drugs from various categories, including but not limited to antifungals, antidiabetics, antihypertensives, antiparasitics, NSAIDs, and antibiotics have been reported to override QS circuitry and QS-regulated virulence pathways in P. aeruginosa through in vitro and in vivo studies. Further, pre-clinical studies with FDA-approved drugs have been substantiated by in silico analysis predicting strong binding affinities to key QS receptors of P. aeruginosa such as LasR, RhlR, and PqsR, underscoring their potential mechanisms of action. Besides, with the well-documented safety profiles, pharmacokinetics, and clinical efficacy of the existing drugs, this repurposing approach streamlines the drug development process, minimizes costs, and accelerates the transition to clinical application. This review underscores the transformative potential of drug repurposing as a cost-effective and sustainable solution to the escalating antimicrobial resistance crisis and advocates for further research to optimize and clinically validate these promising antivirulence therapies.