PXD063129

PXD063129 is an original dataset announced via ProteomeXchange.

Title	Selective silencing of antibiotic--tethered ribosomes as 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 aminoglycoside is 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 clusters 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. This previously unrecognized resistance mechanism—selective silencing of corrupted targets—reveals a novel antibiotic resistance strategy with potential therapeutic implications.
HostingRepository	PanoramaPublic
AnnounceDate	2025-08-29
AnnouncementXML	Submission_2025-08-29_13:25:31.122.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Ingo Wohlgemuth
SpeciesList	scientific name: Escherichia coli K-12; NCBI TaxID: 83333;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-19 21:49:48	ID requested
⏵ 1	2025-08-29 13:25:31	announced

no publication

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

Ingo Wohlgemuth
contact affiliation	Project Group Fidelity of Protein Synthesis in vivo, Department for Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
contact email	ingo.wohlgemuth@mpibpc.mpg.de
lab head
Ingo Wohlgemuth
contact affiliation	Project Group Fidelity of Protein Synthesis in vivo, Department for Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
contact email	ingo.wohlgemuth@mpibpc.mpg.de
dataset submitter

Panorama Public dataset URI