Extracellular vesicle crosstalk in urinary tract infections: Integrating host exosomes and pathogen-derived membrane vesicles for antimicrobial resistance monitoring and diagnostic innovation.

Urinary tract infections (UTIs) remain a major global health burden, with rising antimicrobial resistance (AMR) posing severe challenges to diagnosis and treatment. While host-derived urinary exosomes have been recognized as promising noninvasive biomarkers for UTI, the role of pathogen-derived outer membrane vesicles (OMVs) in UTI pathogenesis and AMR has been comparatively underexplored. No comprehensive framework currently integrates both host extracellular vesicles (EVs) and pathogen-derived EVs in the context of UTI diagnosis and antimicrobial resistance monitoring. This review addresses this gap by synthesizing current evidence on the bidirectional EV crosstalk between uropathogens and host cells during UTI. We examine how host exosomes carry antimicrobial effectors and inflammatory signals, while pathogen OMVs serve as vehicles for horizontal gene transfer of antibiotic resistance genes, enzymatic degradation of antibiotics, and immune evasion. We evaluate the diagnostic potential of dual EV profiling, integrating host exosomal markers such as Akt, CD9, and miR-18a-5p with pathogen OMV markers including beta-lactamases and antibiotic resistance genes, to enable simultaneous UTI diagnosis and AMR prediction. We further discuss emerging microfluidic technologies for rapid EV isolation and characterization, the Target Product Profile and Target Specimen Profile frameworks essential for clinical translation, the role of fit-for-purpose specimen panels from professional biobanks in analytical and clinical validation, and the challenges in translating these findings into clinical practice. By bridging the host-pathogen EV divide, this review proposes a paradigm shift toward integrated extracellular vesicle-based diagnostics that could transform UTI management in the era of antimicrobial resistance.