Bacterial extracellular vesicles: emerging players in antimicrobial resistance and clinical translation.

Antimicrobial resistance (AMR) represents a critical and escalating global health challenge that extends beyond classical genetic mechanisms of resistance acquisition. Increasing evidence highlights extracellular vesicles (EVs) as key mediators of bacterial adaptation, intercellular communication, and resistance dissemination. Among these, bacterial extracellular vesicles (BEVs) play a central role by transporting diverse cargo, including antibiotic resistance genes, mobile genetic elements, antibiotic inactivating enzymes, and immunomodulatory factors. By facilitating horizontal gene transfer (HGT) and non-genetic resistance mechanisms such as antibiotic sequestration, extracellular neutralization, and biofilm reinforcement, BEVs contribute to the emergence and persistence of multidrug-resistant (MDR) infections. This review critically examines the biogenesis, cargo composition, and functional roles of BEVs in bacterial pathogenesis and AMR, while also discussing the complementary influence of host-derived EVs on infection dynamics and antimicrobial responses. We assess emerging evidence supporting EVs as non-invasive biomarkers for resistance surveillance and as adaptable platforms for vaccine development and targeted antimicrobial delivery. Finally, we highlight key unresolved challenges, including vesicle heterogeneity, limited understanding of cargo selection mechanisms, and the lack of standardized isolation and characterization protocols, which must be addressed to enable the clinical and translational integration of EV-based strategies in combating AMR.