PXD007972 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Drug-driven phenotypic convergence supports rational treatment strategies of chronic infections |
Description | Chronic 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:41:34.421.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tune Wulff |
SpeciesList | scientific name: Pseudomonas aeruginosa PAO1; NCBI TaxID: 208964; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Synapt MS |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-10-16 05:37:11 | ID requested | |
1 | 2018-10-23 14:31:46 | announced | |
⏵ 2 | 2024-10-22 04:41:42 | announced | 2024-10-22: 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 affiliation | 1Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Lyngby, Denmark |
contact email | msom@bio.dtu.dk |
lab head | |
Tune Wulff |
contact affiliation | Technical University of Denmark, Novo Nordisk Foundation Center for Biosustainability |
contact email | tuwu@biosustain.dtu.dk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD007972
- Label: PRIDE project
- Name: Drug-driven phenotypic convergence supports rational treatment strategies of chronic infections