{"title":"High-throughput single-cell analysis reveals Omp38-specific monoclonal antibodies that protect against <i>Acinetobacter baumannii</i> infection.","authors":"Yiwei Zhang, Hao Cheng, Peng Yu, Shufeng Wang, Hui Dong, Song Lu, Ruiqi Yang, Baiqing Li, Jie Luo, Ruihan Mao, Zhaohui Zhang, Yong Qi, Xiaohua Chen, Jinya Ding, Zemin He, Jingbo Zhang, Tingting Zhao, Xiangmei Chen, Rong Lin, Haibo Li, Yi Tian, Yuzhang Wu","doi":"10.1080/22221751.2024.2437243","DOIUrl":null,"url":null,"abstract":"<p><p>Infections caused by <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) have emerged as a global public health concern because of high pathogenicity of this bacterium. Monoclonal antibodies (mAbs) have a lower likelihood of promoting drug resistance and offer targeted treatment, thereby reducing potential adverse effects; however, the therapeutic potential of mAbs targeting <i>A. baumanni</i>i has not been fully characterized. In this study, mAbs against the outer membrane proteins (OMPs) of <i>A. baumannii</i> were isolated in a high-throughput manner. The ability of Omp38-specific mAbs to bind to <i>A. baumannii</i> strains from diverse sources was confirmed via enzyme-linked immunosorbent assay (ELISA). Intravenous administration of the Omp38-specific mAbs significantly improved the survival rate and reduced the bacterial load in a mouse model of lethal <i>A. baumannii</i> infection. Flow cytometry and ELISA confirmed that immune cell infiltration and cytokine production, respectively, decreased in a mouse model of sublethal <i>A. baumannii</i> infection. In addition, analysis of the Omp38-mAb C3 binding conformation revealed the potential mechanism of broad-spectrum binding activity of this mAb against <i>A. baumannii</i>. Taken together, these findings indicate that mAbs against Omp38 facilitate bacterial clearance from host, minimize inflammatory mediator release and reduce host damage, highlighting the potential of Omp38-specific mAbs in the clinical treatment of <i>A. baumannii</i> infection.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2437243"},"PeriodicalIF":8.4000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Emerging Microbes & Infections","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/22221751.2024.2437243","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/17 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Infections caused by Acinetobacter baumannii (A. baumannii) have emerged as a global public health concern because of high pathogenicity of this bacterium. Monoclonal antibodies (mAbs) have a lower likelihood of promoting drug resistance and offer targeted treatment, thereby reducing potential adverse effects; however, the therapeutic potential of mAbs targeting A. baumannii has not been fully characterized. In this study, mAbs against the outer membrane proteins (OMPs) of A. baumannii were isolated in a high-throughput manner. The ability of Omp38-specific mAbs to bind to A. baumannii strains from diverse sources was confirmed via enzyme-linked immunosorbent assay (ELISA). Intravenous administration of the Omp38-specific mAbs significantly improved the survival rate and reduced the bacterial load in a mouse model of lethal A. baumannii infection. Flow cytometry and ELISA confirmed that immune cell infiltration and cytokine production, respectively, decreased in a mouse model of sublethal A. baumannii infection. In addition, analysis of the Omp38-mAb C3 binding conformation revealed the potential mechanism of broad-spectrum binding activity of this mAb against A. baumannii. Taken together, these findings indicate that mAbs against Omp38 facilitate bacterial clearance from host, minimize inflammatory mediator release and reduce host damage, highlighting the potential of Omp38-specific mAbs in the clinical treatment of A. baumannii infection.
期刊介绍:
Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses.
The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries.
This journal addresses topics of critical biological and clinical importance, including but not limited to:
- Epidemic surveillance
- Clinical manifestations
- Diagnosis and management
- Cellular and molecular pathogenesis
- Innate and acquired immune responses between emerging microbes and their hosts
- Drug discovery
- Vaccine development research
Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.