Translation error clusters induced by aminoglycoside antibiotics

Ingo Wohlgemuth (), Raffaella Garofalo, Ekaterina Samatova, Aybeg Nafiz Günenç, Christof Lenz, Henning Urlaub () and Marina V. Rodnina ()
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Ingo Wohlgemuth: Max Planck Institute for Biophysical Chemistry
Raffaella Garofalo: Max Planck Institute for Biophysical Chemistry
Ekaterina Samatova: Max Planck Institute for Biophysical Chemistry
Aybeg Nafiz Günenç: Max Planck Institute for Biophysical Chemistry
Christof Lenz: Max Planck Institute for Biophysical Chemistry
Henning Urlaub: Max Planck Institute for Biophysical Chemistry
Marina V. Rodnina: Max Planck Institute for Biophysical Chemistry

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21942-6

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