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-Structure paper
タイトル | Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa. |
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ジャーナル・号・ページ | Cell, Vol. 186, Issue 23, Page 5098-5113.e19, Year 2023 |
掲載日 | 2023年11月9日 |
著者 | Alexander Simonis / Christoph Kreer / Alexandra Albus / Katharina Rox / Biao Yuan / Dmitriy Holzmann / Joana A Wilms / Sylvia Zuber / Lisa Kottege / Sandra Winter / Meike Meyer / Kristin Schmitt / Henning Gruell / Sebastian J Theobald / Anna-Maria Hellmann / Christina Meyer / Meryem Seda Ercanoglu / Nina Cramer / Antje Munder / Michael Hallek / Gerd Fätkenheuer / Manuel Koch / Harald Seifert / Ernst Rietschel / Thomas C Marlovits / Silke van Koningsbruggen-Rietschel / Florian Klein / Jan Rybniker / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:37918395 |
手法 | EM (単粒子) |
解像度 | 4.2 - 4.6 Å |
構造データ | EMDB-16805, PDB-8cr9: EMDB-16807, PDB-8crb: |
由来 |
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キーワード | ANTIMICROBIAL PROTEIN / antibody T3SS Tip protein |