High-throughput single-cell analysis reveals Omp38-specific monoclonal antibodies that protect against Acinetobacter baumannii infection

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

High-throughput single-cell analysis reveals Omp38-specific monoclonal antibodies that protect against Acinetobacter baumannii infection

2025

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.

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