作者
Alexander Simonis,Christoph Kreer,Alexandra Albus,Katharina Rox,Biao Yuan,David Holzmann,J. Wilms,Sophie Zuber,Lisa Kottege,Sandra Winter,Meike Meyer,Kristin Schmitt,Henning Gruell,Sebastian J. Theobald,Anna-Maria Hellmann,Christina Meyer,Meryem S. 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
摘要
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.