%0 Journal Article
%A Simonis, Alexander
%A Kreer, Christoph
%A Albus, Alexandra
%A Rox, Katharina
%A Yuan, Biao
%A Holzmann, Dmitriy
%A Wilms, Joana A.
%A Zuber, Sylvia
%A Kottege, Lisa
%A Winter, Sandra
%A Meyer, Meike
%A Schmitt, Kristin
%A Gruell, Henning
%A Theobald, Sebastian J.
%A Hellmann, Anna-Maria
%A Meyer, Christina
%A Ercanoglu, Meryem Seda
%A Cramer, Nina
%A Munder, Antje
%A Hallek, Michael
%A Fätkenheuer, Gerd
%A Koch, Manuel
%A Seifert, Harald
%A Rietschel, Ernst
%A Marlovits, Thomas
%A van Koningsbruggen-Rietschel, Silke
%A Klein, Florian
%A Rybniker, Jan
%T Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa
%J Cell
%V 186
%N 23
%@ 0092-8674
%C New York, NY
%I Elsevier
%M PUBDB-2024-00412
%P 5098 - 5113
%D 2023
%Z Waiting for fulltext
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37918395
%U <Go to ISI:>//WOS:001116377000001
%R 10.1016/j.cell.2023.10.002
%U https://bib-pubdb1.desy.de/record/601922