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000601922 1001_ $$0P:(DE-HGF)0$$aSimonis, Alexander$$b0$$eCorresponding author
000601922 245__ $$aDiscovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa
000601922 260__ $$aNew York, NY$$bElsevier$$c2023
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000601922 520__ $$aDrug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeutic approaches. Here, we deciphered the B cell and antibody response to the virulence-associated type III secretion system (T3SS) in a cohort of patients chronically infected with PA. Single-cell analytics revealed a diverse B cell receptor repertoire directed against the T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies (mAbs) abrogating T3SS-mediated cytotoxicity. Mechanistic studies involving cryoelectron microscopy identified a surface-exposed C-terminal PcrV epitope as the target of highly neutralizing mAbs with broad activity against drug-resistant PA isolates. These anti-PcrV mAbs were as effective as treatment with conventional antibiotics in vivo. Our study reveals that chronically infected patients represent a source of neutralizing antibodies, which can be exploited as therapeutics against PA.
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000601922 7001_ $$aKreer, Christoph$$b1
000601922 7001_ $$aAlbus, Alexandra$$b2
000601922 7001_ $$aRox, Katharina$$b3
000601922 7001_ $$0P:(DE-H253)PIP1091457$$aYuan, Biao$$b4
000601922 7001_ $$aHolzmann, Dmitriy$$b5
000601922 7001_ $$aWilms, Joana A.$$b6
000601922 7001_ $$aZuber, Sylvia$$b7
000601922 7001_ $$aKottege, Lisa$$b8
000601922 7001_ $$aWinter, Sandra$$b9
000601922 7001_ $$aMeyer, Meike$$b10
000601922 7001_ $$aSchmitt, Kristin$$b11
000601922 7001_ $$aGruell, Henning$$b12
000601922 7001_ $$aTheobald, Sebastian J.$$b13
000601922 7001_ $$aHellmann, Anna-Maria$$b14
000601922 7001_ $$aMeyer, Christina$$b15
000601922 7001_ $$aErcanoglu, Meryem Seda$$b16
000601922 7001_ $$aCramer, Nina$$b17
000601922 7001_ $$aMunder, Antje$$b18
000601922 7001_ $$aHallek, Michael$$b19
000601922 7001_ $$aFätkenheuer, Gerd$$b20
000601922 7001_ $$aKoch, Manuel$$b21
000601922 7001_ $$aSeifert, Harald$$b22
000601922 7001_ $$aRietschel, Ernst$$b23
000601922 7001_ $$0P:(DE-H253)PIP1021412$$aMarlovits, Thomas$$b24
000601922 7001_ $$avan Koningsbruggen-Rietschel, Silke$$b25
000601922 7001_ $$aKlein, Florian$$b26
000601922 7001_ $$0P:(DE-HGF)0$$aRybniker, Jan$$b27$$eCorresponding author
000601922 773__ $$0PERI:(DE-600)2001951-8$$a10.1016/j.cell.2023.10.002$$gVol. 186, no. 23, p. 5098 - 5113.e19$$n23$$p5098 - 5113$$tCell$$v186$$x0092-8674$$y2023
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