Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa
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Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa. / Simonis, Alexander; Kreer, Christoph; Albus, Alexandra; Rox, Katharina; Yuan, Biao; Holzmann, Dmitriy; Wilms, Joana A; Zuber, Sylvia; Kottege, Lisa; Winter, Sandra; Meyer, Meike; Schmitt, Kristin; Gruell, Henning; Theobald, Sebastian J; Hellmann, Anna-Maria; Meyer, Christina; Ercanoglu, Meryem Seda; Cramer, Nina; Munder, Antje; Hallek, Michael; Fätkenheuer, Gerd; Koch, Manuel; Seifert, Harald; Rietschel, Ernst; Marlovits, Thomas C; van Koningsbruggen-Rietschel, Silke; Klein, Florian; Rybniker, Jan.
in: CELL, Jahrgang 186, Nr. 23, 09.11.2023, S. 5098-5113.e19.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa
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 C
AU - van Koningsbruggen-Rietschel, Silke
AU - Klein, Florian
AU - Rybniker, Jan
N1 - Copyright © 2023 Elsevier Inc. All rights reserved.
PY - 2023/11/9
Y1 - 2023/11/9
N2 - 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.
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.
KW - Humans
KW - Antibodies, Bacterial/pharmacology
KW - Cryoelectron Microscopy
KW - Immunoglobulins/metabolism
KW - Pseudomonas aeruginosa/drug effects
KW - Antibodies, Neutralizing
KW - Pseudomonas Infections/drug therapy
U2 - 10.1016/j.cell.2023.10.002
DO - 10.1016/j.cell.2023.10.002
M3 - SCORING: Journal article
C2 - 37918395
VL - 186
SP - 5098-5113.e19
JO - CELL
JF - CELL
SN - 0092-8674
IS - 23
ER -