PXD067947

PXD067947 is an original dataset announced via ProteomeXchange.

Title	Selective silencing of antibiotic-tethered ribosomes as a resistance mechanism against aminoglycosides
Description	Antibiotic resistance is a growing threat, underscoring the need to understand the underlying mechanisms. Aminoglycosides kill bacteria by disrupting translation fidelity, leading to the synthesis of aberrant proteins. Surprisingly, mutations in fusA, a gene encoding translation elongation factor G (EF-G), frequently confer resistance, even though EF-G neither participates in mRNA decoding nor blocks aminoglycoside binding. Here, we show that EF-G resistance variants selectively slow ribosome movement along mRNA when aminoglycosides are bound. This delay increases the chance that the drug dissociates before misreading occurs. Over several elongation cycles, this selective silencing of drug-bound ribosomes prevents error cluster formation, preserving proteome and membrane integrity. As a result, fusA mutations confer resistance early in treatment by preventing self-promoted aminoglycoside uptake. Translation on drug-free ribosomes remains sufficiently rapid to sustain near-normal bacterial growth. The mechanism of selective silencing of corrupted targets reveals a previously unrecognized antibiotic resistance strategy with potential therapeutic implications.
HostingRepository	PRIDE
AnnounceDate	2025-09-05
AnnouncementXML	Submission_2025-09-05_01:37:41.630.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ingo Wohlgemuth
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-01 04:45:42	ID requested
⏵ 1	2025-09-05 01:37:42	announced

Dataset with its publication pending

submitter keyword: Antibiotics, ribosome, EF-G, translocation, fidelity, antibiotic resistance, protein synthesis, proteome integrity, misreading, translation

Ingo Wohlgemuth
contact affiliation	Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
contact email	Ingo.Wohlgemuth@mpinat.mpg.de
lab head
Ingo Wohlgemuth
contact affiliation	Max-Planck Institute for Biophysical chemistry
contact email	ingo.wohlgemuth@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067947
     1. Label: PRIDE project
     2. Name: Selective silencing of antibiotic-tethered ribosomes as a resistance mechanism against aminoglycosides