PXD029140 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Impacts of resistance gene knock-outs on the proteome |
Description | The spread of antibiotic resistance has developed to all known antibiotics. Extended spectrum β-lactamase-producing bacteria are particularly problematic, as they are resistant to a wide range of commonly used antibiotics. Resistance to β-lactams is known to be multifactorial, although the underlying mechanisms generally are poorly understood but critical factors for effective therapy against infections, especially for multi-resistant pathogenic bacteria. In the present study, a plasmid-based homologous recombination system was used to target and delete specific β-lactamase genes (i.e., the blaOXA-1, blaTEM-1 or the ESBL blaCTX-M15) of the clinical strain ESBL Escherichia coli CCUG 73778, generating three “knock-out” clone variants, each one lacking only one of the β-lactamases. The objective was to determine the genotypic impacts of each gene loss on the phenotypic antibiotic resistance and proteome of the bacterium. Quantitative proteomic analyses performed on the three clone variants and the original strain, using tandem mass tags (TMT) and bottom-up liquid chromatography tandem mass spectrometry (LC-MS/MS), after exposure to different concentrations of cefadroxil. Variation of the proteome in each clone variant was determined, to establish the relative importance of each resistance gene and better understand the genetic and proteomic responses and mechanisms of the resistance phenotypes. The knockout of blaCTX-M-15 was observed to have the greatest impact in protein expression, with the knockout of blaOXA-1 also effecting a marked but lower degree of changes. Proteins known to be associated with antibiotic resistance, cell membrane integrity, cellular stress, gene expression and hypothetical/unknown function proteins, among others, demonstrated distinct differences in expression levels (Fold change >1-5 or <-1.5), that may be related to aspects of compensation for the mutant resistance phenotypes. The present study provides a framework to study the impacts of targeted loss of antibiotic resistance genes in clinically relevant strains for understanding the mechanisms of phenotypic antibiotic resistance. |
HostingRepository | PRIDE |
AnnounceDate | 2023-01-04 |
AnnouncementXML | Submission_2023-01-04_04:53:49.434.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | ProteomicsCore Facility |
SpeciesList | scientific name: Escherichia coli; NCBI TaxID: 562; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-10-15 03:21:40 | ID requested | |
⏵ 1 | 2023-01-04 04:53:49 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Escherichia coli,antibiotic resistance, β-lactamase, quantitative proteomics, tandem mass tag, LC-MS/MS |
Contact List
EdwardMoore |
contact affiliation | Professor,Department of Infectious Diseases, University of Gothenburg; Box 480, 40530 Göteborg, Sweden |
contact email | edward.moore@gu.se |
lab head | |
ProteomicsCore Facility |
contact affiliation | SAMBIO Core Facilities, Sahgrenska Academy, University of Gothenburg |
contact email | gupcf@outlook.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD029140
- Label: PRIDE project
- Name: Impacts of resistance gene knock-outs on the proteome