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

Emerg Microbes Infect. 2025 Dec;14(1):2437243. doi: 10.1080/22221751.2024.2437243. Epub 2024 Dec 17.

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.

Keywords: Acinetobacter baumannii; Beacon; monoclonal antibody; outer membrane protein.

MeSH terms

  • Acinetobacter Infections* / immunology
  • Acinetobacter Infections* / microbiology
  • Acinetobacter Infections* / prevention & control
  • Acinetobacter baumannii* / immunology
  • Animals
  • Antibodies, Bacterial* / immunology
  • Antibodies, Monoclonal* / administration & dosage
  • Antibodies, Monoclonal* / immunology
  • Bacterial Outer Membrane Proteins* / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Single-Cell Analysis*

Substances

  • Antibodies, Monoclonal
  • Bacterial Outer Membrane Proteins
  • Antibodies, Bacterial
  • Cytokines

Grants and funding

This work was supported by grants from the General Program of the National Natural Science Foundation of China (no. 32170887 and No. 31970885), the Special Program of the National Natural Science Foundation of China (no. 32141005), and the Major Research Plan of the National Natural Science Foundation of China (no. 92269110). Special fund for performance incentive guidance of research institutions in Chongqing (cstc2021jxjl130036) and Chongqing International Institute for Immunology Project (2022YJC01). The funders had no role in the study design, data analyses, or decision to publish.