Newly Identified FDA-Approved MTAs: Opportunities for Antimicrobial Repurposing?

The emergence of antimicrobial resistance represents a major global health challenge, highlighting the urgent need for new therapeutic strategies. Drug repurposing, particularly through the evaluation of FDA-approved compounds with well-established pharmacological profiles, offers a promising avenue. In this study, we performed a phenotypic screening of 31 FDA-approved compounds recently identified as potent Microtubule-Targeting Agents (MTAs) to evaluate their antimicrobial potential. Using agar well diffusion assays, we tested these compounds against selected human pathogenic bacterial and fungal strains. Our results provide the first evidence that several MTAs possess previously unrecognized antimicrobial activities. Of the 31 compounds screened, 18 exhibited inhibitory effects against at least one bacterial or fungal strain, identifying MTAs as potential antimicrobial leads for further investigation. Notably, auranofin, a gold-based antirheumatic agent, consistently displayed antimicrobial activity across all tested strains. Flupentixol dihydrochloride demonstrated selective antifungal inhibition, while mefloquine hydrochloride showed broad-spectrum antibacterial effects. These findings suggest that anti-tubulin activity may contribute to the antifungal effects observed, whereas the possible involvement of FtsZ in the antibacterial activity remains speculative. Further studies, including minimum inhibitory concentration (MIC) determinations, cytotoxicity and selectivity assessments, and mechanistic analyses, are needed to validate these findings and evaluate their potential for antimicrobial repurposing.