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PXD017971-2

PXD017971 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe lytic polysaccharide monooxygenase of Pseudomonas aeruginosa promotes bacterial survival during systemic infection
DescriptionLytic polysaccharide monooxygenases (LPMOs) are a recently discovered enzyme family that cleave polysaccharides by oxidation. Despite proposed roles in bacterial virulence, no direct functional data exist to validate these claims. Here we show that CpbD, the LPMO of the opportunistic pathogen Pseudomonas aeruginosa (PA) is a virulence factor that promotes survival of the bacterium in whole human blood. CbpD was also shown to cleave the glycosidic bonds of the model substrate by an oxidative reaction, a feature that promoted by azurin and pyocyanin. Two redox-active virulence factors co-secreted with the LPMO. Combination of homology modelling, molecular dynamics simulations and small angle X-ray scattering demonstrated that CbpD is a monomeric tri-modular enzyme with highly flexible domain linkers, where domain positioning may be influenced by post translational modifications. Deletion of cbpD rendered P. aeruginosa unable to establish a lethal systemic infection and enhanced bacterial clearance in vivo. Improved bacterial survival of the wildtype was not attributable to dampening of pro-inflammatory responses by the protein, either ex vivo or in vivo. Further quantification of complement products in whole human blood revealed that CbpD reduced the performance of the terminal complement cascade. Importantly, CbpD inactivation by active site mutations abolished both enzyme activity in vitro and function ex vivo, indicating that ligand oxidation is crucial for CbpD virulence function. Finally, profiling of the bacterial and splenic proteome showed that the lack of this single enzyme resulted in substantial re-organization of the bacterial defense systems in vitro and the targeting of distinct host proteins/pathways in vivo.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:18:15.449.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMagnus Arntzen
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Pseudomonas aeruginosa; NCBI TaxID: 287; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-03-10 06:54:21ID requested
12021-01-28 00:24:51announced
22024-10-22 05:18:15announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: LPMO, virulence, mice,Pseudomonas aeruginosa, spleen
Contact List
Gustav Vaaje-Kolstad
contact affiliationFaculty of Chemistry, Biotechnology and Food Science Norwegian University of Life Sciences Post Office Box 5003 1432, Ås Norway
contact emailgustav.vaaje-kolstad@nmbu.no
lab head
Magnus Arntzen
contact affiliationNorwegian University of Life Sciences
contact emailmagnus.arntzen@nmbu.no
dataset submitter
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