Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa

  • Alexander Simonis (Shared first author)
  • Christoph Kreer (Shared first author)
  • Alexandra Albus
  • Katharina Rox
  • Biao Yuan
  • Dmitriy Holzmann
  • Joana A Wilms
  • Sylvia Zuber
  • Lisa Kottege
  • Sandra Winter
  • Meike Meyer
  • Kristin Schmitt
  • Henning Gruell
  • Sebastian J Theobald
  • Anna-Maria Hellmann
  • Christina Meyer
  • Meryem Seda Ercanoglu
  • Nina Cramer
  • Antje Munder
  • Michael Hallek
  • Gerd Fätkenheuer
  • Manuel Koch
  • Harald Seifert
  • Ernst Rietschel
  • Thomas C Marlovits
  • Silke van Koningsbruggen-Rietschel
  • Florian Klein (Shared last author)
  • Jan Rybniker (Shared last author)

Abstract

Drug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeutic approaches. Here, we deciphered the B cell and antibody response to the virulence-associated type III secretion system (T3SS) in a cohort of patients chronically infected with PA. Single-cell analytics revealed a diverse B cell receptor repertoire directed against the T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies (mAbs) abrogating T3SS-mediated cytotoxicity. Mechanistic studies involving cryoelectron microscopy identified a surface-exposed C-terminal PcrV epitope as the target of highly neutralizing mAbs with broad activity against drug-resistant PA isolates. These anti-PcrV mAbs were as effective as treatment with conventional antibiotics in vivo. Our study reveals that chronically infected patients represent a source of neutralizing antibodies, which can be exploited as therapeutics against PA.

Bibliographical data

Original languageEnglish
ISSN0092-8674
DOIs
Publication statusPublished - 09.11.2023

Comment Deanary

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PubMed 37918395