PXD061583-1

PXD061583 is an original dataset announced via ProteomeXchange.

Title	Selective silencing of antibiotic-tethered ribosomes as a resistance mechanism against aminoglycosides
Description	Understanding antibiotic resistance is essential for combating drug-resistant pathogens. Many bacteria horizontally acquire enzymes that modify antibiotics or their targets to prevent interaction, but when resistance emerges without such modifications, the underlying mechanisms often remain unknown. Here, we describe how mutations in the fusA gene, which encodes translation elongation factor G (EF-G), drive resistance against aminoglycoside antibiotics. fusA resistance mutations, found throughout EF-G, confer resistance without disrupting AGA binding to the ribosome. EF-G resistance variants selectively slow down translocation on aminoglycoside-bound ribosomes until the drug dissociates. This slowdown prevents antibiotic-induced incorporation of consecutive incorrect amino acids (error clusters) into proteins, preserving the proteome and membrane integrity, and limiting drug uptake. In contrast, translocation on antibiotic-free ribosomes remains sufficiently rapid to support near-normal cell growth with or without antibiotic. This previously unrecognized resistance concept—selective silencing of corrupted targets—offers new insights into antibiotic resistance mechanisms beyond traditional paradigms.
HostingRepository	PRIDE
AnnounceDate	2025-08-28
AnnouncementXML	Submission_2025-08-28_15:44:08.937.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	2025-03-07 08:21:48	ID requested
⏵ 1	2025-08-28 15:44:09	announced

Dataset with its publication pending

submitter keyword: proteomics,Antibiotic resistance, ribosome, protein synthesis, misreading

Dr Ingo Wohlgemuth
contact affiliation	Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11 37077 Goetttingen
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

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/2025/08/PXD061583

PRIDE project URI

• PRIDE
  1. PXD061583
     1. Label: PRIDE project
     2. Name: Selective silencing of antibiotic-tethered ribosomes as a resistance mechanism against aminoglycosides