Repurposing Finasteride and Serotonin Reuptake Inhibitors as Novel Antimicrobials: A Dual-Action Approach to Target Bacterial and Fungal Pathogens

Background: The global rise of antimicrobial resistance necessitates the development of innovative therapeutic strategies beyond traditional antibiotics. Drug repurposing offers a time- and cost-effective approach by identifying new antimicrobial applications for existing medications. Thus, this study aimed to investigate the antimicrobial and anti-virulence potential of several clinically approved drugs, including fluconazole, buspirone, duloxetine, escitalopram, and finasteride. Methods: We evaluated the antimicrobial efficacy of the selected compounds against a panel of microorganisms comprising two Gram-negative bacteria (Escherichia coli, Serratia marcescens), two Gram-positive bacteria (Bacillus megaterium, Staphylococcus epidermidis), and two opportunistic yeasts (Candida albicans, Rhodotorula mucilaginosa). Antimicrobial activity was evaluated using growth inhibition and viability assays. Additionally, we investigated the effects of the selected drugs on fungal virulence traits, including biofilm formation and filamentation, and assessed infectivity using a Caenorhabditis elegans host model. Results: Duloxetine and escitalopram demonstrated broad-spectrum antimicrobial activity, inhibiting bacterial and fungal growth at concentrations below 512 mg/L. Buspirone exhibited selective antimicrobial effects, particularly against Gram-positive bacteria and C. albicans. Although finasteride exhibited limited direct antifungal activity, it significantly disrupted key virulence traits in yeasts, including biofilm formation, morphological transitions, and host infection capacity. Conclusion: These findings underscore the potential of serotonin reuptake inhibitors and finasteride as candidates for antimicrobial repurposing. By impairing both microbial viability and pathogenicity, these drugs may provide promising avenues for developing adjunct or alternative therapies against resistant bacterial and fungal pathogens.