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This crisis demands innovative therapeutic strategies that transcend traditional antibiotic paradigms. Within this context, exosomes, naturally secreted nanoscale extracellular vesicles, have emerged as compelling therapeutic alternatives and delivery vehicles. These endogenous phospholipid bilayer vesicles carry diverse bioactive cargo derived from their parent cells, facilitating direct antibacterial effects while actively orchestrating host immunomodulation through antigen presentation and immune response regulation. This multifaceted functionality positions exosomes as potent tools capable of not only eradicating pathogens but also modulating the complex host\u2013pathogen interface and enhancing host defenses. This review systematically evaluates the burgeoning role of exosomes in combating bacterial infections. The fundamental methodologies for isolating, characterizing and classifying exosomes relevant to infectious disease research are summarized. Subsequently, we critically analyze their intrinsic antibacterial properties and explore advanced engineered therapeutic mechanisms. The discussion further examines innovative strategies integrating exosomes with complementary treatments and details their preclinical applications across diverse infection pathologies. Finally, we outline key translational challenges and future research directions essential for advancing the development of next-generation antibacterial exosomes with enhanced efficacy and reduced off-target toxicity.<\/jats:p>","DOI":"10.1093\/rb\/rbag137","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:44:25Z","timestamp":1781783065000},"source":"Crossref","is-referenced-by-count":1,"title":["Biofluid-derived exosomes as next-generation biotherapeutic platforms to combat multidrug-resistant bacterial infections"],"prefix":"10.1093","volume":"13","author":[{"given":"Anqi","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine , Zhengzhou 450006,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haohang","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Chemical Engineering, Fuzhou University , Fuzhou 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