TY  - JOUR
AU  - Simonis, Alexander
AU  - Kreer, Christoph
AU  - Albus, Alexandra
AU  - Rox, Katharina
AU  - Yuan, Biao
AU  - Holzmann, Dmitriy
AU  - Wilms, Joana A.
AU  - Zuber, Sylvia
AU  - Kottege, Lisa
AU  - Winter, Sandra
AU  - Meyer, Meike
AU  - Schmitt, Kristin
AU  - Gruell, Henning
AU  - Theobald, Sebastian J.
AU  - Hellmann, Anna-Maria
AU  - Meyer, Christina
AU  - Ercanoglu, Meryem Seda
AU  - Cramer, Nina
AU  - Munder, Antje
AU  - Hallek, Michael
AU  - Fätkenheuer, Gerd
AU  - Koch, Manuel
AU  - Seifert, Harald
AU  - Rietschel, Ernst
AU  - Marlovits, Thomas
AU  - van Koningsbruggen-Rietschel, Silke
AU  - Klein, Florian
AU  - Rybniker, Jan
TI  - Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa
JO  - Cell
VL  - 186
IS  - 23
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - PUBDB-2024-00412
SP  - 5098 - 5113
PY  - 2023
N1  - Waiting for fulltext
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37918395
UR  - <Go to ISI:>//WOS:001116377000001
DO  - DOI:10.1016/j.cell.2023.10.002
UR  - https://bib-pubdb1.desy.de/record/601922
ER  -