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  Translation error clusters induced by aminoglycoside antibiotics

Wohlgemuth, I., Garofalo, R., Samatova, E. N., Günenç, A. N., Lenz, C., Urlaub, H., et al. (2021). Translation error clusters induced by aminoglycoside antibiotics. Nature Communications, 12: 1830. doi:10.1038/s41467-021-21942-6.

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 Creators:
Wohlgemuth, I.1, Author              
Garofalo, R.2, Author              
Samatova, E. N.2, Author              
Günenç, A. N.2, Author              
Lenz, C.3, Author              
Urlaub, H.4, Author              
Rodnina, M. V.1, Author              
Affiliations:
1Department of Physical Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578598              
2Department of Physical Biochemistry, MPI for Biophysical Chemistry, Max Planck Society, ou_578598              
3Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              
4Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: Antibiotics; Mass spectrometry; Mechanism of action; Ribosome
 Abstract: Aminoglycoside antibiotics target the ribosome and induce mistranslation, yet which translation errors induce bacterial cell death is unclear. The analysis of cellular proteins by quantitative mass spectrometry shows that bactericidal aminoglycosides induce not only single translation errors, but also clusters of errors in full-length proteins in vivo with as many as four amino acid substitutions in a row. The downstream errors in a cluster are up to 10,000-fold more frequent than the first error and independent of the intracellular aminoglycoside concentration. The prevalence, length, and composition of error clusters depends not only on the misreading propensity of a given aminoglycoside, but also on its ability to inhibit ribosome translocation along the mRNA. Error clusters constitute a distinct class of misreading events in vivo that may provide the predominant source of proteotoxic stress at low aminoglycoside concentration, which is particularly important for the autocatalytic uptake of the drugs.

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Language(s): eng - English
 Dates: 2021-03-23
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-021-21942-6
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Title: Nature Communications
Source Genre: Journal
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Pages: 14 Volume / Issue: 12 Sequence Number: 1830 Start / End Page: - Identifier: -