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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.
Afiliação
  • Simonis A; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for I
  • Kreer C; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Albus A; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Rox K; Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, 38124 Braunschweig, Germany.
  • Yuan B; Institute of Structural and Systems Biology, University Medical Center Hamburg-Eppendorf (UKE), 22607 Hamburg, Germany; Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany; Deutsches Elektronen-Synchrotron Zentrum (DESY), 22607 Hamburg, Germany.
  • Holzmann D; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Wilms JA; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Zuber S; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Kottege L; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Winter S; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Meyer M; CF Centre, Pediatric Pulmonology and Allergology, University Children's Hospital Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Centre for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Co
  • Schmitt K; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Gruell H; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, G
  • Theobald SJ; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Hellmann AM; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Department of Experimental Pediatric Oncology, University Children's Hospital Cologne, Faculty of Medicine and University Hospital Cologne, University of
  • Meyer C; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Ercanoglu MS; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Cramer N; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany.
  • Munder A; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, 30625 Hannover, Germany.
  • Hallek M; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Fätkenheuer G; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; German Center for Infection Research (DZIF), partner site Bonn-Cologne, 50937 Cologne, Germany.
  • Koch M; Institute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Seifert H; German Center for Infection Research (DZIF), partner site Bonn-Cologne, 50937 Cologne, Germany; Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50935 Cologne, Germany.
  • Rietschel E; CF Centre, Pediatric Pulmonology and Allergology, University Children's Hospital Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Centre for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Co
  • Marlovits TC; Institute of Structural and Systems Biology, University Medical Center Hamburg-Eppendorf (UKE), 22607 Hamburg, Germany; Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany; Deutsches Elektronen-Synchrotron Zentrum (DESY), 22607 Hamburg, Germany.
  • van Koningsbruggen-Rietschel S; CF Centre, Pediatric Pulmonology and Allergology, University Children's Hospital Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Centre for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Co
  • Klein F; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research (DZIF), partner site Bonn-Cologne, 50937 Cologne, Germany; Laboratory of Experimental Immunology, Institute of Virolo
  • Rybniker J; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for I
Cell ; 186(23): 5098-5113.e19, 2023 11 09.
Article em En | MEDLINE | ID: mdl-37918395
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Infecções por Pseudomonas / Anticorpos Neutralizantes / Anticorpos Antibacterianos Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Infecções por Pseudomonas / Anticorpos Neutralizantes / Anticorpos Antibacterianos Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article