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PXD007972

PXD007972 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDrug-driven phenotypic convergence supports rational treatment strategies of chronic infections
DescriptionChronic Pseudomonas aeruginosa infections evades antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P.aeruginosa towards clinically relevant antibiotics leads to phenotypic convergence towards distinct states. These states are associated with collateral sensitivity towards several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In depth investigation of chronic P.aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic convergence. Notably, fluoroquinolone-resistant subpopulations harboring nfxB mutations were eradicated by antibiotic therapy as predicted by our in vitro data. This study supports the hypothesis that antibiotic treatment of chronic infections can be optimized by targeting phenotypic states associated with specific mutations to improve treatment success in chronic infections.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:41:34.421.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTune Wulff
SpeciesList scientific name: Pseudomonas aeruginosa PAO1; NCBI TaxID: 208964;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-10-16 05:37:11ID requested
12018-10-23 14:31:46announced
22024-10-22 04:41:42announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.cell.2017.12.012;
Imamovic L, Ellabaan MMH, Dantas Machado AM, Citterio L, Wulff T, Molin S, Krogh Johansen H, Sommer MOA, Drug-Driven Phenotypic Convergence Supports Rational Treatment Strategies of Chronic Infections. Cell, 172(1-2):121-134.e14(2018) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: Collateral sensitivity, cystic fibrosis, nfxB, chronic infections, phenotypic convergence, drug resistance, Pseudomonas aeruginosa
Contact List
Morten Otto Alexander Sommer
contact affiliation1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Lyngby, Denmark
contact emailmsom@bio.dtu.dk
lab head
Tune Wulff
contact affiliationTechnical University of Denmark, Novo Nordisk Foundation Center for Biosustainability
contact emailtuwu@biosustain.dtu.dk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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