Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa

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.

• 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.
• Hallek, M.
• Fätkenheuer, G.
• Koch, M.
• Seifert, H.
• Rietschel, E.
• Marlovits, T. C.
• van Koningsbruggen-Rietschel, S.
• Klein, F.
• Rybniker, J.