Dynamic Profiling of Penicillin‐Binding Protein 2a (PBP2a)‐Positive Extracellular Vesicles: Implications for Early Diagnosis and Treatment Monitoring of Methicillin‐Resistant Staphylococcus Aureus Infections

作者：Qianqian Gao, Wenwu Zhou, Zhen Shen, Tianchi Chen, Cong Hu, Liang Dong, Da Han, Min Li · 发表于：Journal of Extracellular Vesicles · 年份：2025 · DOI：10.1002/jev2.70111 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、Bacterial Infections and Vaccines、Cell Adhesion Molecules Research

ABSTRACT Infections caused by methicillin‐resistant staphylococci (MRS), such as methicillin‐resistant Staphylococcus aureus (MRSA), pose significant challenges to public health. The early detection of MRS infections and monitoring of antibiotic resistance profiles are critical for patient management and infection control strategies. Extracellular vesicles (EVs) have emerged as promising biomarkers in infectious disease. By combining single‐particle nano‐flow cytometry and immunoelectron microscopy (immuno‐TEM), we discovered that PBP2a is present on the surface of EVs extracted from MRS. However, whether PBP2a can serve as an EVs‐associated protein marker for diagnosing bacterial infections remains unexplored. Using MRSA as a model strain, mouse models of localized and systemic infections were established, alongside a clinical cohort study, to investigate the dynamics of PBP2a‐positive (PBP2a + ) EVs in plasma following bacterial infection, infection progression, and in response to antimicrobial therapy. In mouse infection models, PBP2a + EVs were detected in plasma, with variable detection rates observed across different infection models. The study found a progressive correlation between increasing plasma PBP2a + EVs levels and non‐specific inflammation markers (CRP, IL‐6) during infection progression. Antimicrobial therapies, however, inversely affected the ratio of PBP2a + EVs. Furthermore, a clinical cohort study confirmed a direct association between the magnitude of PB...