From Biogenesis to Host Modulation: The Expanding Biology of Oral Streptococcal Membrane Vesicles

Abstract Bacterial extracellular membrane vesicles (bEVs) provide fundamental biological functions through communication, ecological adaptation, and mediation of host interactions. Gram-positive oral streptococci were long considered to be incapable of bEVs production due to their thick peptidoglycan. In contrast, recent advances in imaging, biochemical isolation, and multi-omics profiling have revealed that bEVs production is common and may represent a general trait of streptococci. This review summarizes current research on the biogenesis, cargo composition, and functional roles of bEVs, with an emphasis on oral streptococcal vesicles and their contributions to oral microbial ecology and host responses. We highlight methodological innovations for isolation and characterization of bEVs that have led to the discovery of species-specific bEVs cargo. Functionally, bEVs participate in diverse biological activities, including horizontal gene transfer, antimicrobial peptide delivery, virulence and redox modulation, and they profoundly influence host immunity by modulating cytokine signaling, epithelial barrier function, and immune pathways. Emerging evidence further suggests active roles in polymicrobial biofilm development and systemic dissemination of microbial signals relevant to health and disease. By integrating biochemical, structural, ecological, and immunological perspectives, this review provides a comprehensive overview of the current state of streptococcal and Gram-positive bEVs research and discusses its translational potential to support oral and general health.