PXD027810 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Targeting the fitness cost of antibiotic resistance via the non-essential genome |
Description | Mutations in the rifampicin (Rif)-binding site of RNA polymerase (RNAP) impart antibiotic resistance and inextricably affect transcription initiation, elongation, and termination properties as well. At each step of the transcription cycle, RNAP responds to non-essential transcription factors, signaling molecules, and substrate availability. As such, the non- essential genome and its impact on fitness cost potentially represent an untapped resource for new combination therapies. Using transposon sequencing (Tn-seq), we present a genome- wide analysis of resistance cost in a clinically common rpoB H526Y mutant. Our data show that cost-compounding genes include factors that promote high transcription elongation rate, whereas cost-mitigating genes function in cell wall synthesis and division. We demonstrate that cell wall synthesis and division defects in rpoB H526Y are a consequence of an abnormally high transcription elongation rate, which is further exacerbated by superfluous activity of the uracil salvage pathway and indifference of the mutant RNAP to alarmone ppGpp. Leveraging on this knowledge, we identified drugs that are highly potent against rpoB H526Y and other RifR alleles from the same phenotypic class. Thus, genome-wide analysis of fitness cost of antibiotic resistant mutants should expedite discovery of new combination therapies and delineate cellular pathways that underlie molecular mechanisms of cost. |
HostingRepository | PRIDE |
AnnounceDate | 2021-11-25 |
AnnouncementXML | Submission_2021-11-25_07:46:18.573.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Nikita Vasilyev |
SpeciesList | scientific name: Escherichia coli; NCBI TaxID: 562; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-08-09 06:33:49 | ID requested | |
⏵ 1 | 2021-11-25 07:46:19 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: antibiotic resistance, rifampicin, RNA polymerase, fitness cost |
Contact List
Evgeny Nudler |
contact affiliation | Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, US |
contact email | evgeny.nudler@nyulangone.org |
lab head | |
Nikita Vasilyev |
contact affiliation | NYU School of Medicine |
contact email | nikita.vasilyev@nyulangone.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027810
- Label: PRIDE project
- Name: Targeting the fitness cost of antibiotic resistance via the non-essential genome