A plasmid-associated immunoglobulin-binding protein in Acinetobacter baumannii
TL;DR
This study demonstrates ImbA as an unrecognised plasmid-encoded virulence factor in A. baumannii that drives immune evasion and hypervirulence by intercepting host immunoglobulins, highlighting ImbA as a non-antibiotic therapeutic target with potential against multidrug-resistant A. baumannii.
Abstract
Summary Background Acinetobacter baumannii is a critical global health threat due to multidrug resistance and high mortality. Although antimicrobial resistance mechanisms are well characterised, the virulence determinants that drive severe infections remain poorly understood. Methods We screened 89 carbapenem-resistant clinical isolates of A. baumannii for virulence in animal infection models and combined comparative genomics with functional assays to identify virulence factors. An immunoglobulin-binding protein from A. baumannii (ImbA) encoded on the type D plasmid was selected and characterised. Protein–immunoglobulin interactions were analysed by pull-down and biolayer interferometry. Additional ImbA inhibition of IgG–Fcγ receptor binding by flow cytometry were tested. Protective efficacy was evaluated in mice using vaccination or anti-ImbA antibodies. Findings A type D plasmid was consistently linked to high virulence in clinical isolates. The deletion of plasmid-encoded ImbA attenuated virulence. ImbA bound murine IgA and IgG with high affinity. The binding to the Fc region of IgG disrupted IgG–Fcγ receptor interactions. Vaccination with recombinant ImbA improved survival and reduced bacterial dissemination in female mice with anti-ImbA antibodies partially protecting against lethal infection. Bacterial burdens in the blood were reduced in treated groups. Interpretation Our study demonstrates ImbA as an unrecognised plasmid-encoded virulence factor in A. baumannii. By intercepting host immunoglobulins, ImbA drives immune evasion and hypervirulence. Blocking ImbA by vaccination and antibody therapy restored host defence and improved outcomes in female mice, highlighting ImbA as a non-antibiotic therapeutic target with potential against multidrug-resistant A. baumannii. Funding Bio&Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (MSIT) (No. RS-2023-00219213); Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program.