Journal Article

PUBDB-2024-00412

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa

Simonis, A. (Corresponding author) ; Kreer, C. ; Albus, A. ; Rox, K. ; Yuan, B.CSSB*DESY* ; Holzmann, D. ; Wilms, J. A. ; Zuber, S. ; Kottege, L. ; Winter, S. ; Meyer, M. ; Schmitt, K. ; Gruell, H. ; Theobald, S. J. ; Hellmann, A.-M. ; Meyer, C. ; Ercanoglu, M. S. ; Cramer, N. ; Munder, A. ; Hallek, M. ; Fätkenheuer, G. ; Koch, M. ; Seifert, H. ; Rietschel, E. ; Marlovits, T.CSSB*DESY* ; van Koningsbruggen-Rietschel, S. ; Klein, F. ; Rybniker, J. (Corresponding author)

2023
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.cell.2023.10.002

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.

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Contributing Institute(s):

1. CSSB-UKE-TM (CSSB-UKE-TM)
2. Strukturelle Mikrobiologie CSSB (FS-CS)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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