PXD007972

PXD007972 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biomedical

submitter keyword: Collateral sensitivity, cystic fibrosis, nfxB, chronic infections, phenotypic convergence, drug resistance, Pseudomonas aeruginosa

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/10/PXD007972

PRIDE project URI

• PRIDE
  1. PXD007972
     1. Label: PRIDE project
     2. Name: Drug-driven phenotypic convergence supports rational treatment strategies of chronic infections