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PXD011568

PXD011568 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleResource misallocation as a mediator of fitness costs in antibiotic resistance
DescriptionAntimicrobial resistance (AMR) poses a threat to global health and the economy. Rifampicin resistant Mycobacterium tuberculosis accounts for a third of the global AMR burden. Gaining the upper hand on AMR requires a deeper understanding of the physiology of resistance. AMR often results in the erosion of normal cell function: a fitness cost. Identifying intervention points in the mechanisms underpinning the cost of resistance in M. tuberculosis could play a pivotal role in strengthening future treatment regimens. We used a collection of M. tuberculosis strains providing an evolutionary and phylogenetic snapshot of rifampicin resistance and subjected them to genome-wide transcriptomic and proteomic profiling to identify key perturbations of normal physiology. We found that a rifampicin resistance-conferring mutation in RpoB imparts considerable gene expression changes, many of which are mitigated by a compensatory mutation in RpoC. However, our data also provide evidence for pervasive epistasis: the same resistance mutation imposed a different fitness cost and functionally unrelated changes to gene expression in clinical strains from unrelated genetic backgrounds. Rather than functional changes in specific pathways, our data suggest that the fitness cost of rifampicin resistance stems from a misallocation of resources: the greater the departure from the wild type baseline proteome investment, the greater the fitness cost of rifampicin resistance in a given strain. We summarize these observations in the “Burden of Expression” hypothesis of fitness cost and provide evidence that it can be used for suppressing the emergence of rifampicin resistance.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:19:57.725.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAmir Banaei-Esfahani
SpeciesList scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-11-02 02:51:54ID requested
12021-03-12 03:26:44announced
22024-10-22 05:19:58announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biomedical
submitter keyword: Genomics, Clinical Isolates,Mycobacterium tuberculosis, Systems Biology, Transcriptomics, Drug Resistance, Proteomics
Contact List
Ruedi Aebersold
contact affiliationInstitute of Molecular Systems Biology, ETH Zurich, Switzerland
contact emailaebersold@imsb.biol.ethz.ch
lab head
Amir Banaei-Esfahani
contact affiliationETH Zurich
contact emailamir.banaei@gmail.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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