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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, Vol. 186, No. 23, 09.11.2023, p. 5098-5113.e19.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Simonis, A, Kreer, C, Albus, A, Rox, K, Yuan, B, Holzmann, D, Wilms, JA, Zuber, S, Kottege, L, Winter, S, Meyer, M, Schmitt, K, Gruell, H, Theobald, SJ, Hellmann, A-M, Meyer, C, Ercanoglu, MS, Cramer, N, Munder, A, Hallek, M, Fätkenheuer, G, Koch, M, Seifert, H, Rietschel, E, Marlovits, TC, van Koningsbruggen-Rietschel, S, Klein, F & Rybniker, J 2023, 'Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa', CELL, vol. 186, no. 23, pp. 5098-5113.e19. https://doi.org/10.1016/j.cell.2023.10.002

APA

Simonis, A., Kreer, C., Albus, A., Rox, K., Yuan, B., 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., ... Rybniker, J. (2023). Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa. CELL, 186(23), 5098-5113.e19. https://doi.org/10.1016/j.cell.2023.10.002

Vancouver

Simonis A, Kreer C, Albus A, Rox K, Yuan B, Holzmann D et al. Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa. CELL. 2023 Nov 9;186(23):5098-5113.e19. https://doi.org/10.1016/j.cell.2023.10.002

Bibtex

@article{fff57be9c826419ab5e250367bee665c,
title = "Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa",
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.",
keywords = "Humans, Antibodies, Bacterial/pharmacology, Cryoelectron Microscopy, Immunoglobulins/metabolism, Pseudomonas aeruginosa/drug effects, Antibodies, Neutralizing, Pseudomonas Infections/drug therapy",
author = "Alexander Simonis and Christoph Kreer and Alexandra Albus and Katharina Rox and Biao Yuan and Dmitriy Holzmann and Wilms, {Joana A} and Sylvia Zuber and Lisa Kottege and Sandra Winter and Meike Meyer and Kristin Schmitt and Henning Gruell and Theobald, {Sebastian J} and Anna-Maria Hellmann and Christina Meyer and Ercanoglu, {Meryem Seda} and Nina Cramer and Antje Munder and Michael Hallek and Gerd F{\"a}tkenheuer and Manuel Koch and Harald Seifert and Ernst Rietschel and Marlovits, {Thomas C} and {van Koningsbruggen-Rietschel}, Silke and Florian Klein and Jan Rybniker",
note = "Copyright {\textcopyright} 2023 Elsevier Inc. All rights reserved.",
year = "2023",
month = nov,
day = "9",
doi = "10.1016/j.cell.2023.10.002",
language = "English",
volume = "186",
pages = "5098--5113.e19",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "23",

}

RIS

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 -