PXD011568

PXD011568 is an original dataset announced via ProteomeXchange.

Title	Resource misallocation as a mediator of fitness costs in antibiotic resistance
Description	Antimicrobial 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:19:57.725.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amir Banaei-Esfahani
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-02 02:51:54	ID requested
1	2021-03-12 03:26:44	announced
⏵ 2	2024-10-22 05:19:58	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Genomics, Clinical Isolates,Mycobacterium tuberculosis, Systems Biology, Transcriptomics, Drug Resistance, Proteomics

Ruedi Aebersold
contact affiliation	Institute of Molecular Systems Biology, ETH Zurich, Switzerland
contact email	aebersold@imsb.biol.ethz.ch
lab head
Amir Banaei-Esfahani
contact affiliation	ETH Zurich
contact email	amir.banaei@gmail.com
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/2021/03/PXD011568

PRIDE project URI

• PRIDE
  1. PXD011568
     1. Label: PRIDE project
     2. Name: Resource misallocation as a mediator of fitness costs in antibiotic resistance