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dc.contributor.authorAskarian, Fatemeh
dc.contributor.authorUchiyama, Satoshi
dc.contributor.authorMasson, Helen
dc.contributor.authorSørensen, Henrik Vinther
dc.contributor.authorGolten, Ole
dc.contributor.authorBunæs, Anne Cathrine
dc.contributor.authorMekasha, Sophanit
dc.contributor.authorRøhr, Åsmund Kjendseth
dc.contributor.authorKommedal, Eirik Garpestad
dc.contributor.authorLudviksen, Judith Anita
dc.contributor.authorArntzen, Magnus Øverlie
dc.contributor.authorSchmidt, Benjamin
dc.contributor.authorZurich, Raymond H.
dc.contributor.authorVan Sorge, Nina M.
dc.contributor.authorEijsink, Vincent
dc.contributor.authorKrengel, Ute
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorLewis, Nathan E.
dc.contributor.authorNizet, Victor
dc.contributor.authorVaaje-Kolstad, Gustav
dc.date.accessioned2021-03-04T09:37:47Z
dc.date.available2021-03-04T09:37:47Z
dc.date.issued2021-02-23
dc.description.abstractThe recently discovered lytic polysaccharide monooxygenases (LPMOs), which cleave polysaccharides by oxidation, have been associated with bacterial virulence, but supporting functional data is scarce. Here we show that CbpD, the LPMO of <i>Pseudomonas aeruginosa</i>, is a chitin-oxidizing virulence factor that promotes survival of the bacterium in human blood. The catalytic activity of CbpD was promoted by azurin and pyocyanin, two redox-active virulence factors also secreted by <i>P. aeruginosa</i>. Homology modeling, molecular dynamics simulations, and small angle X-ray scattering indicated that CbpD is a monomeric tri-modular enzyme with flexible linkers. Deletion of <i>cbpD</i> rendered <i>P. aeruginosa</i> unable to establish a lethal systemic infection, associated with enhanced bacterial clearance in vivo. CbpD-dependent survival of the wild-type bacterium was not attributable to dampening of pro-inflammatory responses by CbpD ex vivo or in vivo. Rather, we found that CbpD attenuates the terminal complement cascade in human serum. Studies with an active site mutant of CbpD indicated that catalytic activity is crucial for virulence function. Finally, profiling of the bacterial and splenic proteomes showed that the lack of this single enzyme resulted in substantial re-organization of the bacterial and host proteomes. LPMOs similar to CbpD occur in other pathogens and may have similar immune evasive functions.en_US
dc.identifier.citationAskarian F, Uchiyama S, Masson, Sørensen HV, Golten O, Bunæs AC, Mekasha S, Røhr ÅK, Kommedal E, Ludviksen, Arntzen M, Schmidt, Zurich, Van Sorge NM, Eijsink V, Krengel U, Mollnes, Lewis NE, Nizet V, Vaaje-Kolstad G. The lytic polysaccharide monooxygenase CbpD promotes Pseudomonas aeruginosa virulence in systemic infection. Nature Communications. 2021en_US
dc.identifier.cristinIDFRIDAID 1893724
dc.identifier.doihttps://doi.org/10.1038/s41467-021-21473-0
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/10037/20643
dc.language.isoengen_US
dc.publisherNature Researchen_US
dc.relation.journalNature Communications
dc.relation.projectIDNorges forskningsråd: 272201en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIBIO2/249865/Norway/Discovering novel functions of carbohydrate-active enzymes to unravel novel mechanisms of bacterial virulence//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleThe lytic polysaccharide monooxygenase CbpD promotes Pseudomonas aeruginosa virulence in systemic infectionen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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