Details

Autor(en) / Beteiligte

• 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

Titel

Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa

Ist Teil von

• Cell, 2023-11, Vol.186 (23), p.5098-5113.e19

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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.