Monoclonal antibodies protect against pandrug-resistant Klebsiella pneumoniae.
basic_science · Level V
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- Record sourced from PubMed, PMID 41034577.
- Also identified by DOI 10.1038/s41586-025-09391-3.
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Abstract
The 'silent pandemic' caused by antimicrobial resistance requires innovative therapeutic approaches. Human monoclonal antibodies (mAbs), which are among the most transformative and safe drugs in oncology<sup>1</sup> and autoimmunity<sup>2</sup>, are rarely used for infectious diseases and not yet used for antimicrobial resistance<sup>3</sup>. Here we applied an antigen-agnostic strategy to isolate extremely potent human mAbs against Klebsiella pneumoniae sequence type 147 (ST147), a hypervirulent and pandrug-resistant lineage that is spreading globally. Isolated mAbs target the KL64 capsule and the O-antigen. However, although mAbs displayed bactericidal activity in the picomolar range in vitro, only the capsule-specific mAbs were protective against fulminant bloodstream infection by ST147 and two geographically and genetically distant carbapenem-resistant KL64-bearing K. pneumoniae. Protection observed in vivo correlated with in vitro bacterial uptake by macrophages and enchained bacterial growth. Our study thus describes a mAb that protects against pandrug-resistant K. pneumoniae and provides a strategy to isolate mAbs and identify mAbs that confer protection against bacteria with antimicrobial resistance.
Medical subject headings
- Klebsiella pneumoniae
- Antibodies, Monoclonal
- Klebsiella Infections
- Drug Resistance, Multiple, Bacterial
- Drug Resistance, Bacterial