Proteomic advances in extracellular vesicles: unlocking biomarkers for microbial infectious diseases.

INTRODUCTION: Microbial infectious diseases pose a significant threat to global health. Early and accurate pathogen identification directly influences antimicrobial strategies and patient outcomes. Extracellular vesicles (EVs) serve as key mediators of intercellular signaling and can transport nucleic acids and proteins from both host and pathogen sources. Proteomic analysis of EVs captures pathogen activity, host response, and tissue injury, offering a review-focused perspective on biomarker discovery for microbial infectious diseases. AREAS COVERED: This review summarizes the biogenesis and major classifications of EVs. Using a 'dual-track' strategy that examines both pathogen-derived and host-response-induced EVs, we discuss protein alterations associated with viral and bacterial infections and explore their potential clinical value as biomarkers. We also summarize the technologies used across the cited literature and discuss the remaining challenges in translating EV proteins into diagnostic biomarkers for microbial infectious diseases. EXPERT OPINION: Proteomics has been widely used to identify biomarkers of infection and inflammation. EV-associated protein alterations are closely associated with microbial infectious disease progression and may reflect pathogen-derived signals, host immune changes, and organ injury. Clinical translation will require standardized EV isolation, reproducible mass-spectrometry workflows, targeted validation, and rapid assay formats suitable for point-of-care testing.