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@ARTICLE{Simonis:601922,
author = {Simonis, Alexander and Kreer, Christoph and Albus,
Alexandra and Rox, Katharina and Yuan, Biao and Holzmann,
Dmitriy and Wilms, Joana A. and Zuber, Sylvia and Kottege,
Lisa and Winter, Sandra and Meyer, Meike and Schmitt,
Kristin and Gruell, Henning and Theobald, Sebastian J. and
Hellmann, Anna-Maria and Meyer, Christina and Ercanoglu,
Meryem Seda and Cramer, Nina and Munder, Antje and Hallek,
Michael and Fätkenheuer, Gerd and Koch, Manuel and Seifert,
Harald and Rietschel, Ernst and Marlovits, Thomas and van
Koningsbruggen-Rietschel, Silke and Klein, Florian and
Rybniker, Jan},
title = {{D}iscovery of highly neutralizing human antibodies
targeting {P}seudomonas aeruginosa},
journal = {Cell},
volume = {186},
number = {23},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {PUBDB-2024-00412},
pages = {5098 - 5113},
year = {2023},
note = {Waiting for fulltext},
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.},
cin = {CSSB-UKE-TM / FS-CS},
ddc = {610},
cid = {I:(DE-H253)CSSB-UKE-TM-20210520 /
I:(DE-H253)FS-CS-20210408},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633)},
pid = {G:(DE-HGF)POF4-633},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37918395},
UT = {WOS:001116377000001},
doi = {10.1016/j.cell.2023.10.002},
url = {https://bib-pubdb1.desy.de/record/601922},
}