Journal of Extracellular Vesicles最新文献

{"title":"Development of Broadly Applicable Reference EVs Expressing Horseradish Peroxidase","authors":"Daniela Waas,&nbsp;Marc Juraschitz,&nbsp;Yen-Fu Adam Chen,&nbsp;Harald Waltenberger,&nbsp;Wolfgang Hammerschmidt,&nbsp;Reinhard Zeidler,&nbsp;Sonja Molinaro,&nbsp;Kathrin Gärtner","doi":"10.1002/jev2.70115","DOIUrl":"https://doi.org/10.1002/jev2.70115","url":null,"abstract":"<p>Extracellular vesicles (EVs) hold great promise as circulating biomarkers for diagnostic and therapeutic approaches. Thus, many research groups world-wide investigate important aspects of EVs including their biology and medical significance. For this, a large number of procedures and protocols has been established making it difficult to almost impossible to compare and replicate results. Consequently, diagnostic tests remain problematic to interpret, mainly because the use of reliable reference EVs as a qualified standard has not yet gained widespread acceptance. Beyond doubt, such reference EVs are key to assess EV preparations quantitatively and to establish robust quality control processes to ensure overall quality and validity of data. To further advance the establishment of such controls, we designed and generated a new class of reference EVs expressing horseradish peroxidase (HRP) to facilitate simple and reliable EV tracing during isolation and standardization of EV purification and downstream analysis processes. HRP⁺ EVs can be quantified easily and with unmatched sensitivity either directly via measuring HRP activity or indirectly via immunodetection of HRP on the EV surface. We demonstrate that HRP⁺ EVs allow the reliable quantification of absolute EV numbers in biological or medical samples to normalize clinical specimens in liquid biopsies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic Devices for Manufacture of Therapeutic Extracellular Vesicles: Advances and Opportunities","authors":"Amin Hassanzadeh-Barforoushi,&nbsp;Xenia Sango,&nbsp;Ella L. Johnston,&nbsp;David Haylock,&nbsp;Yuling Wang","doi":"10.1002/jev2.70132","DOIUrl":"https://doi.org/10.1002/jev2.70132","url":null,"abstract":"<p>Extracellular vesicles (EVs) are emerging as promising candidates in therapeutic applications due to their unique ability to mediate intercellular communication and deliver biological cargo. With increasing interest in EV-based therapies, the development of scalable, cost-effective and regulatory-compliant production methods is critical. Microfluidic platforms offer transformative potential in EV manufacturing, providing precise control over production conditions, enhanced purity and seamless integration with quality control systems. This review highlights the advantages of microfluidic technologies in EV production, including fine-tuning of shear stress to optimise yield, advanced purification strategies that achieve high recovery and purity, and on-chip capabilities for EV loading and surface modification. Key challenges such as scaling up production while maintaining sterility, controlling EV release after immunoaffinity capture, and addressing clogging and fouling in microfluidic devices are discussed alongside emerging solutions. Additionally, the integration of AI-driven automation and real-time monitoring, as well as personalised EV manufacturing, is explored as pivotal innovations. Future directions emphasise the potential of combining size- and affinity-based methods for EV isolation and aligning microfluidic technologies with regulatory requirements to accelerate clinical translation. Therefore, we believe microfluidics platforms for EV isolation hold immense potential to redefine EV manufacturing by enabling scalable, reproducible and high-quality production systems essential for therapeutic applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tethered Exosomes Containing the Matrix Metalloproteinase MT1-MMP Contribute to Extracellular Matrix Degradation","authors":"Roberta Palmulli,&nbsp;Hannah K. Jackson,&nbsp;James R. Edgar","doi":"10.1002/jev2.70122","DOIUrl":"https://doi.org/10.1002/jev2.70122","url":null,"abstract":"<p>For cancer cells to escape from the primary tumour and metastasize, they must degrade and navigate through the extracellular matrix (ECM). The transmembrane protease MT1-matrix metalloprotease (MMP) plays a key role in localized matrix degradation, and its overexpression promotes cancer invasion. In this study, we demonstrate that MT1-MMP is trafficked to the intraluminal vesicles of multivesicular endosomes, and subsequently released from cells on exosomes, a subtype of extracellular vesicle that can be retained to the surface of the originating cell by the anti-viral restriction factor, tetherin. Although tetherin overexpression is linked to increased cell migration and invasion in various cancers, its role in these processes remains unclear. Our findings reveal that expression of tetherin by breast cancer cells promotes the retention of MT1-MMP-positive exosomes at their cell surface, while tetherin loss enhances exosome escape and impairs ECM degradation. Thus, tethered exosomes promote the retention of MT1-MMP at the surface of cells, aiding the degradation of the ECM and promoting cancer cell invasion.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling a Novel Mechanism of Enhanced Secretion, Cargo Loading, and Accelerated Dynamics of Bacterial Extracellular Vesicles Following Antibiotic Exposure","authors":"Jinpeng Li,&nbsp;Chao Li,&nbsp;Yun Han,&nbsp;Yulian Hu,&nbsp;Jian Yang,&nbsp;Heting Xu,&nbsp;Xinggui Chen,&nbsp;Ming Yang,&nbsp;Jing Zuo,&nbsp;Yizhi Tang,&nbsp;Changwei Lei,&nbsp;Cui Li,&nbsp;Hongning Wang","doi":"10.1002/jev2.70131","DOIUrl":"https://doi.org/10.1002/jev2.70131","url":null,"abstract":"<p>Antibiotic exposure substantially alters the production mechanisms of bacterial extracellular vesicles (BEVs), which serve as carriers for intercellular exchange of DNA, proteins, and nutrients, yet the underlying mechanisms remain elusive. Here, using <i>Escherichia coli</i> as a model, we uncover how antibiotic exposure enhances BEV secretion, cargo enrichment, and motility. Our results demonstrate that enrofloxacin (ENR) triggers the SOS response, leading to upregulation of the endolysin genes <i>essd-1</i>, <i>rrrd</i>, and <i>rzod</i>, causing peptidoglycan layer damage and promoting modest BEV formation with encapsulated bioactive components such as DNA and proteins. More critically, ENR suppresses <i>ompR</i>, a key regulator in the OmpR/EnvZ two-component system, downregulating the expression of the outer membrane (OM) protein OmpC and its associated Mla-OmpC lipopolysaccharide transport complex. This destabilization of the OM further facilitates BEV formation and cargo encapsulation. The Δ<i>ompR</i> mutant in <i>E. coli</i> also exhibits reduced type I fimbriae and enhanced BEV motility, indicating that the OmpR/EnvZ system modulates BEV dynamics via type I fimbriae regulation. These findings reveal a novel mechanism by which <i>E. coli</i> adapts to sub-inhibitory antibiotic stress by modulating BEV formation and motility, with implications for biomedical nanodelivery applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK-Cell-Derived Extracellular Vesicles Engineered to Carry Senolytics Eliminate Chemotherapy-Induced Senescent Osteosarcoma Cells","authors":"Xianlin Yue,&nbsp;Jie Cui,&nbsp;Shifeng Ren,&nbsp;Yajun Zhang,&nbsp;Ying Li,&nbsp;Hongjuan Cui,&nbsp;Johnny Huard,&nbsp;Paul D. Robbins,&nbsp;Xiaodong Mu","doi":"10.1002/jev2.70123","DOIUrl":"https://doi.org/10.1002/jev2.70123","url":null,"abstract":"<p>Osteosarcoma (OS) is a type of bone tumour characterized by high risk of metastatic progression and recurrence after therapy. Traditional tumour treatment methods such as radiotherapy and chemotherapy can lead to the accumulation of senescent cells in tumours. Treatment-induced senescence (TIS) can lead to incomplete tumour clearance and potential recurrence. Recently, the combination of chemotherapy drugs and senolytics drugs (‘one-two punch’ therapy) has become a promising strategy for improved tumour treatment, but this method also faces challenges in terms of safety and targeting specificity. In order to further improve the efficacy of chemotherapy on OS, here we developed a senolytic drug delivery system based on engineered Natural killer (NK) cell-derived extracellular vesicles (EVs) that can target OS cells. EVs were engineered to contain doxorubicin (Dox), termed iRGD-EVs-Dox, and used to induce cellular senescence in OS cells, followed by delivery of the Bcl-2 family inhibitor ABT-263 in similar engineered EVs (iRGD-EVs-ABT-263), to specifically eliminate the senescent OS cells induced by Dox. Our results demonstrate that iRGD-EVs have efficient targeting ability to OS cells and iRGD-EVs-ABT-263 effectively induced senolysis of Dox-induced senescent OS cells in vitro and repressed tumour growth in OS cell xenograft mouse models. Taken together, our results demonstrate the therapeutic efficiency of using engineered EVs from NK cells to deliver first a chemotherapeutic agent to induce senescent OS cells followed by a senolytic drug to eliminate chemotherapy-induced senescent OS cells, providing a novel strategy for more effective cancer treatment.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Clinical Scale MSC-Derived Extracellular Vesicles Enhance Poststroke Neuroplasticity in Rodents and Non-Human Primates”","authors":"","doi":"10.1002/jev2.70135","DOIUrl":"https://doi.org/10.1002/jev2.70135","url":null,"abstract":"<p>Kim EH, Son JP, Oh GS, et al. 2025. “Clinical Scale MSC-Derived Extracellular Vesicles Enhance Poststroke Neuroplasticity in Rodents and Non-Human Primates”. Journal of Extracellular Vesicles 14, no. 6: e70110. https://doi.org/10.1002/jev2.70110</p><p>In the originally published article, the funding entity for Eun Hee Kim, Gyun Sik Oh and Suji Park was given incorrectly as S&amp;E bio, Inc. The correct funding information is given below.</p><p><b>Funding</b>: S&amp;E bio Co., Ltd., provided support for this study in the form of salaries for Eun Hee Kim, Gyun Sik Oh, and Suji Park.</p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small EVs From Adipose-Derived MSCs Modulate Epidermal Barrier and Inflammation Via Sphingosine-1-Phosphate Signaling Pathway","authors":"Kyong-Oh Shin,&nbsp;Jun Ho Lee,&nbsp;Seungwoo Chae,&nbsp;Karin Goto,&nbsp;Hahyun An,&nbsp;Joan S. Wakefield,&nbsp;Dae Hyun Ha,&nbsp;Healim Lee,&nbsp;Kyojin Lee,&nbsp;Hyunju Lee,&nbsp;Ella Shin,&nbsp;Min Ji Kang,&nbsp;Sinhee Lee,&nbsp;Yoshikazu Uchida,&nbsp;Byong Seung Cho,&nbsp;Kyungho Park","doi":"10.1002/jev2.70121","DOIUrl":"https://doi.org/10.1002/jev2.70121","url":null,"abstract":"<p>Epidermal permeability barrier defects are associated with several skin diseases, including atopic dermatitis (AD). Using an AD mouse model, we previously demonstrated that topically administered small extracellular vesicles (sEVs) (prepared following the International Society of Extracellular Vesicles recommendations) from human adipose tissue-derived mesenchymal stem cells (ASC) ameliorate skin inflammation and normalize barrier function in parallel with increased ceramide (a key barrier lipid) production. To elucidate <i>how</i> ASC-sEVs alleviate these AD skin abnormalities, we characterized lipids and ceramide metabolic enzymes in ASC-sEVs versus donor ASCs. Our study revealed that free fatty acid, ceramide, and sphingomyelin are enriched in ASC-sEVs versus donor ASCs, while the synthetic enzymes of ceramide (and acidic sphingomyelinase), and sphingosine-1-phosphate (sphingosine kinase) are significantly higher in ASC-sEVs versus donor ASCs. Conversely, ceramide (ceramidase), and sphingosine-1-phosphate hydrolytic enzymes (sphingosine-1-phosphate lyase and sphingosine-1-phosphate phosphatase) are lower in ASC-sEVs, suggesting that ceramide and sphingosine-1-phosphate levels could elevate in cells that receive ASC-sEVs. ASC-sEV-mediated increases in sphingosine-1-phosphate suppress pro-inflammatory cytokine production in AD-model human keratinocytes. Additionally, keratinocyte differentiation, which is required for a competent epidermal permeability barrier, was restored in AD-model human keratinocytes treated with ASC-sEVs. Taken together, cells that endocytose ASC-sEVs can normalize epidermal permeability barrier function as well as alleviate inflammation by stimulating a sphingosine-1-phosphate signalling pathway.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Extracellular Vesicles Identifies CDCP1 as Critical Metastasis-Related Glycoprotein in Lung Cancer","authors":"Lu Zhang,&nbsp;Yan Wu,&nbsp;Suntao Li,&nbsp;Miao Guo,&nbsp;Jiaqi Zhao,&nbsp;Chengxi Cao,&nbsp;Yan Zhang,&nbsp;Hua Xiao","doi":"10.1002/jev2.70128","DOIUrl":"https://doi.org/10.1002/jev2.70128","url":null,"abstract":"<p>Lung cancer is the most prevalent malignancy worldwide, with the majority of fatalities attributed to metastasis. Recent studies have demonstrated the pivotal role of extracellular vesicles (EVs) and glycoproteins in tumor progression. In this study, we compared the glycoproteome of EVs from 95C (low metastatic) and 95D (high metastatic) lung cancer cells to discover key targets in metastasis. Through coupling lectin affinity chromatography with quantitative proteomics, 1562 glycoproteins were identified. Compared to 95C EVs, 23 glycoproteins were significantly upregulated more than 20-fold in 95D EVs, including CDCP1, TNC, NCAM2, and ITGA4. CUB-domain containing protein 1 (CDCP1) was upregulated 143-fold in 95D EVs, which is significantly correlated with poor prognosis of lung cancer patients in the TCGA database. We subsequently performed site-specific glycoform profiling of CDCP1 using intact glycopeptide enrichment. Then we generated <i>CDCP1</i> knockout (KO) 95D cell lines and revealed that the absence of CDCP1 reduced cell migration ability, which was also confirmed by EVs and cell co-culture experiments. We further performed Ti⁴⁺-IMAC-based phosphoproteomic analysis to investigate the changes in signaling pathways in <i>CDCP1</i> KO cell lines. 147 differentially expressed phosphoproteins were revealed. Verification experiments confirmed that the levels of phosphorylated SRC and JUN proteins, markers of ErbB signaling pathway, were decreased 5.5-fold and 4.2-fold, respectively. Glycosylation site mutagenesis identified N339 and N386 as critical functional determinants of CDCP1. Collectively, our data demonstrate that glycoprotein CDCP1 was selectively packed into EVs and potentially contributed to cancer metastasis, which is a critical target for anti-metastasis research and cancer therapy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles Derived From Streptococcus anginosus Aggravate Lupus Nephritis by Triggering TLR2-MyD88-NF-κB Signalling in NK Cells","authors":"Ying Gong,&nbsp;Lingyue Jin,&nbsp;Lina Duan,&nbsp;Jie Xiao,&nbsp;Yao Li,&nbsp;HongXia Wang,&nbsp;Haifang Wang,&nbsp;Wanying Lin,&nbsp;Yi Zhang,&nbsp;Xiufeng Gan,&nbsp;Shuyin Pang,&nbsp;Yurong Qiu,&nbsp;Weinan Lai,&nbsp;Lei Zheng,&nbsp;Haixia Li","doi":"10.1002/jev2.70134","DOIUrl":"https://doi.org/10.1002/jev2.70134","url":null,"abstract":"<p>Systemic lupus erythematosus (SLE) has been linked to gut microbiome dysbiosis, notably an overabundance of <i>Streptococcus anginosus</i>; however, the impact of this microbial imbalance on disease pathogenesis remains unclear. Here, we investigated the contribution of <i>S. anginosus</i>-derived extracellular vesicles (<i>SA</i>-EVs) to SLE progression, with an emphasis on lupus nephritis (LN). Fifty-four SLE patients and 43 healthy controls (HC) were recruited. The faecal, blood and serum samples from participants were collected. SLE disease activity (SLEDA) was evaluated by the SLEDA Index (SLEDAI). Stool <i>S. anginosus</i> abundance was quantified by quantitative PCR, NK cell activation by flow cytometry and serum proinflammatory cytokines profile by ELISA. Lupus-prone MRL/lpr mice were orally administered <i>SA</i>-EVs to evaluate in vivo inflammatory responses, renal NK cell activation and renal histopathological changes. <i>S. anginosus</i> levels were significantly elevated in SLE patients relative to HC, positively correlated with SLEDAI scores and NK cell cytotoxicity. In vitro, <i>SA</i>-EVs stimulation of patient NK cells significantly heightened proinflammatory mediator production (granzyme B, TNF-α), increased cytotoxicity and downregulated inhibitory receptors (TIM-3, NKG2A, TIGIT) compared to control EVs from <i>S. Salivarius</i> (<i>SS</i>-EVs). Mechanistically, lipoteichoic acid (LTA) within <i>SA</i>-EVs engaged Toll-like receptor 2 (TLR2) on NK cells, activating MyD88/NF-κB signalling pathway. In MRL/lpr mice, <i>SA</i>-EVs treatment increased renal immune complex deposition, upregulated renal NK cell activation markers (NKp44, NKp46), and exacerbated LN pathology with greater immune cell infiltration and inflammatory cytokine levels. Furthermore, NK cell depletion with anti-NK1.1 antibodies significantly prolonged survival in <i>SA</i>-EVs administered mice. Thus, <i>SA</i>-EVs exacerbate SLE by hyperactivating NK cells via the TLR2-MyD88-NF-κB pathway, leading to amplified systemic inflammation and aggravated LN. These findings underscore the potential of targeting <i>SA</i>-EVs for therapeutic intervention in SLE.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Profiling of Penicillin-Binding Protein 2a (PBP2a)-Positive Extracellular Vesicles: Implications for Early Diagnosis and Treatment Monitoring of Methicillin-Resistant Staphylococcus Aureus Infections","authors":"Qianqian Gao,&nbsp;Wenwu Zhou,&nbsp;Zhen Shen,&nbsp;Tianchi Chen,&nbsp;Cong Hu,&nbsp;Liang Dong,&nbsp;Da Han,&nbsp;Min Li","doi":"10.1002/jev2.70111","DOIUrl":"https://doi.org/10.1002/jev2.70111","url":null,"abstract":"<p>Infections caused by methicillin-resistant staphylococci (MRS), such as methicillin-resistant <i>Staphylococcus aureus</i> (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 PBP2a⁺ EVs in the plasma of patients with MRSA infection and the severity of infection. The investigation highlights the potential of PBP2a⁺ EVs as plasma biomarkers of MRSA antibiotic resistance, particularly during the early stages of resistant infections. Their persistence in plasma throughout the infectious episode makes them valuable indicators for monitoring disease progression and evaluating the efficacy of antibiotic treatments.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 7","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}