Bacterial extracellular vesicles in priority pathogens: Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae

Antimicrobial resistance (AMR) is a major global health threat that requires innovative approaches to infection prevention and treatment. In 2024, the World Health Organization (WHO) updated its Bacterial Priority Pathogens List (BPPL) to guide research toward the pathogens of highest clinical relevance. Among these, carbapenem-resistant Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and macrolide-resistant Streptococcus pneumoniae remain major contributors to infectious disease burden and AMR-associated mortality worldwide. Recent evidence identifies bacterial extracellular vesicles (bEVs) as important mediators of microbial adaptation, host interaction, and antimicrobial resistance. Released under physiological and stress conditions, bEVs carry proteins, lipids, and nucleic acids that can influence bacterial survival and infection outcomes. In this mini-review, we summarize current knowledge on bEVs produced by these WHO priority pathogens and discuss their emerging roles in infection biology. We highlight how bEVs contribute to antimicrobial resistance through the transport of resistance-associated proteins, the horizontal transfer of resistance genes and antibiotic-degrading activity. We further examine the involvement of bEVs in inflammation, host tissue damage and immune modulation, including their capacity to carry virulence factors or sequester antimicrobial agents. Finally, we discuss recent advances in the use of bEVs as vaccine platforms. We prioritize studies on extracellular vesicles (EVs) from antibiotic-resistant strains of the three WHO priority pathogens. When these were unavailable, we also included studies using antibiotic-susceptible strains, particularly for S. pneumoniae, for which data on macrolide-resistant strains are lacking. Overall, bEVs are increasingly recognized as active components of bacterial physiology and promising targets for developing new strategies against antimicrobial-resistant infections.