Congratulations to Christoph and the Rybniker lab on our latest study published in Cell
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.
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* and Jan Rybniker*, Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa; Cell, November 2023