8cr9
Cryo-EM structure of PcrV/Fab(30-B8)
Structural highlights
FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.G3XD49_PSEAE Publication Abstract from PubMedDrug-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. Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa.,Simonis A, Kreer C, Albus A, Rox K, Yuan B, Holzmann D, Wilms JA, Zuber S, Kottege L, Winter S, Meyer M, Schmitt K, Gruell H, Theobald SJ, Hellmann AM, Meyer C, Ercanoglu MS, Cramer N, Munder A, Hallek M, Fatkenheuer G, Koch M, Seifert H, Rietschel E, Marlovits TC, van Koningsbruggen-Rietschel S, Klein F, Rybniker J Cell. 2023 Nov 9;186(23):5098-5113.e19. doi: 10.1016/j.cell.2023.10.002. Epub , 2023 Nov 1. PMID:37918395[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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