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TitleDiscovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa.
Journal, issue, pagesCell, Vol. 186, Issue 23, Page 5098-5113.e19, Year 2023
Publish dateNov 9, 2023
AuthorsAlexander Simonis / Christoph Kreer / Alexandra Albus / Katharina Rox / Biao Yuan / Dmitriy Holzmann / Joana A Wilms / Sylvia Zuber / Lisa Kottege / Sandra Winter / Meike Meyer / Kristin Schmitt / Henning Gruell / Sebastian J Theobald / Anna-Maria Hellmann / Christina Meyer / Meryem Seda 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 /
PubMed AbstractDrug-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 ...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.
External linksCell / PubMed:37918395
MethodsEM (single particle)
Resolution4.2 - 4.6 Å
Structure data

16805

8cr9

EMDB-16805, PDB-8cr9:
Cryo-EM structure of PcrV/Fab(30-B8)
Method: EM (single particle) / Resolution: 4.2 Å

16807

8crb

EMDB-16807, PDB-8crb:
Cryo-EM structure of PcrV/Fab(11-E5)
Method: EM (single particle) / Resolution: 4.6 Å

Source
  • homo sapiens (human)
  • pseudomonas aeruginosa (bacteria)
KeywordsANTIMICROBIAL PROTEIN / antibody T3SS Tip protein

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