dc.date.accessioned | 2021-04-23T19:46:49Z | |
dc.date.available | 2021-04-23T19:46:49Z | |
dc.date.created | 2021-02-25T14:20:42Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Askarian, Fatemeh Uchiyama, Satoshi Masson, Helen Sørensen, Henrik Vinther Golten, Ole Bunæs, Anne Cathrine Mekasha, Sophanit Røhr, Åsmund Kjendseth Kommedal, Eirik Garpestad Ludviksen, Judith Anita Arntzen, Magnus Øverlie Schmidt, Benjamin Zurich, Raymond H. Van Sorge, Nina M. Eijsink, Vincent Krengel, Ute Mollnes, Tom Eirik Lewis, Nathan E. Nizet, Victor Vaaje-Kolstad, Gustav . The lytic polysaccharide monooxygenase CbpD promotes Pseudomonas aeruginosa virulence in systemic infection. Nature Communications. 2021 | |
dc.identifier.uri | http://hdl.handle.net/10852/85513 | |
dc.description.abstract | Abstract The 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 Pseudomonas aeruginosa , 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 P. aeruginosa . 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 c bpD rendered P. aeruginosa 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. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | The lytic polysaccharide monooxygenase CbpD promotes Pseudomonas aeruginosa virulence in systemic infection | |
dc.type | Journal article | |
dc.creator.author | Askarian, Fatemeh | |
dc.creator.author | Uchiyama, Satoshi | |
dc.creator.author | Masson, Helen | |
dc.creator.author | Sørensen, Henrik Vinther | |
dc.creator.author | Golten, Ole | |
dc.creator.author | Bunæs, Anne Cathrine | |
dc.creator.author | Mekasha, Sophanit | |
dc.creator.author | Røhr, Åsmund Kjendseth | |
dc.creator.author | Kommedal, Eirik Garpestad | |
dc.creator.author | Ludviksen, Judith Anita | |
dc.creator.author | Arntzen, Magnus Øverlie | |
dc.creator.author | Schmidt, Benjamin | |
dc.creator.author | Zurich, Raymond H. | |
dc.creator.author | Van Sorge, Nina M. | |
dc.creator.author | Eijsink, Vincent | |
dc.creator.author | Krengel, Ute | |
dc.creator.author | Mollnes, Tom Eirik | |
dc.creator.author | Lewis, Nathan E. | |
dc.creator.author | Nizet, Victor | |
dc.creator.author | Vaaje-Kolstad, Gustav | |
cristin.unitcode | 185,15,12,63 | |
cristin.unitname | Seksjon for kjemisk livsvitenskap - biomolekyler, bio-inspirerte materialer og bioanalytisk kjemi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1893724 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature Communications&rft.volume=&rft.spage=&rft.date=2021 | |
dc.identifier.jtitle | Nature Communications | |
dc.identifier.volume | 12 | |
dc.identifier.issue | 1 | |
dc.identifier.doi | https://doi.org/10.1038/s41467-021-21473-0 | |
dc.identifier.urn | URN:NBN:no-88173 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2041-1723 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/85513/2/Askarian_Nat%2BCommun%2B2021.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 1230 | |
dc.relation.project | NFR/272201 | |
dc.relation.project | NFR/240967 | |
dc.relation.project | NFR/208896 | |
dc.relation.project | NFR/245828 | |
dc.relation.project | NFR/249865 | |