Efflux modulation as an antimicrobial strategy: mechanisms and translational perspectives

Efflux pumps are widely viewed as antibiotic resistance determinants, yet their roles in stress adaptation, virulence, quorum sensing, and biofilm formation make them context-dependent therapeutic targets. This Perspective distinguishes four efflux intervention strategies: direct inhibition, bioenergetic or membrane-mediated suppression, regulatory modulation, and dual-effect approaches. We examine why promising in vitro findings rarely translate clinically and argue that efflux-targeting strategies require defined therapeutic objectives and integrated multidisciplinary approaches.