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dc.contributor.authorAskarian, Fatemeh
dc.contributor.authorTsai, Chih-Ming
dc.contributor.authorCordara, Gabriele
dc.contributor.authorZurich, Raymond H.
dc.contributor.authorBjånes, Elisabet
dc.contributor.authorGolten, Ole
dc.contributor.authorSørensen, Henrik Vinther
dc.contributor.authorKousha, Armin
dc.contributor.authorMeier, Angela
dc.contributor.authorChikwati, Elvis Mashingaidze
dc.contributor.authorBruun, Jack-Ansgar
dc.contributor.authorLudviksen, Judith K
dc.contributor.authorChoudhury, Biswa
dc.contributor.authorTrieu, Desmond
dc.contributor.authorDavis, Stanley
dc.contributor.authorEdvardsen, Per Kristian Thorén
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorLiu, George Y.
dc.contributor.authorKrengel, Ute
dc.contributor.authorConrad, Douglas J.
dc.contributor.authorVaaje-Kolstad, Gustav
dc.contributor.authorNizet, Victor
dc.date.accessioned2023-09-18T06:41:58Z
dc.date.available2023-09-18T06:41:58Z
dc.date.issued2023-07-17
dc.description.abstractPseudomonas aeruginosa (PA) CbpD belongs to the lytic polysaccharide monooxygenases (LPMOs), a family of enzymes that cleave chitin or related polysaccharides. Here, we demonstrate a virulence role of CbpD in PA pneumonia linked to impairment of host complement function and opsonophagocytic clearance. Following intratracheal challenge, a PA ΔCbpD mutant was more easily cleared and produced less mortality than the wild-type parent strain. The x-ray crystal structure of the CbpD LPMO domain was solved to subatomic resolution (0.75Å) and its two additional domains modeled by small-angle X-ray scattering and Alphafold2 machine-learning algorithms, allowing structure-based immune epitope mapping. Immunization of naive mice with recombinant CbpD generated high IgG antibody titers that promoted human neutrophil opsonophagocytic killing, neutralized enzymatic activity, and protected against lethal PA pneumonia and sepsis. IgG antibodies generated against full-length CbpD or its noncatalytic M2+CBM73 domains were opsonic and protective, even in previously PA-exposed mice, while antibodies targeting the AA10 domain were not. Preexisting antibodies in PA-colonized cystic fibrosis patients primarily target the CbpD AA10 catalytic domain. Further exploration of LPMO family proteins, present across many clinically important and antibiotic-resistant human pathogens, may yield novel and effective vaccine antigens.en_US
dc.identifier.citationAskarian, Tsai, Cordara, Zurich, Bjånes, Golten, Sørensen, Kousha, Meier, Chikwati, Bruun, Ludviksen, Choudhury, Trieu, Davis, Edvardsen, Mollnes, Liu, Krengel, Conrad, Vaaje-Kolstad, Nizet. Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumonia. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(30)en_US
dc.identifier.cristinIDFRIDAID 2175345
dc.identifier.doi10.1073/pnas.2301538120
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttps://hdl.handle.net/10037/31036
dc.language.isoengen_US
dc.publisherNational Academy of Scienceen_US
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)en_US
dc.titleImmunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumoniaen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)