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Cell ; 186(23): 5098-5113.e19, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37918395

RESUMO

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.


Assuntos
Anticorpos Antibacterianos , Anticorpos Neutralizantes , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Anticorpos Antibacterianos/farmacologia , Microscopia Crioeletrônica , Imunoglobulinas/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Infecções por Pseudomonas/tratamento farmacológico
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