Dataset Information

Translation Error Clusters Induced by Aminoglycoside Antibiotics

ABSTRACT: Aminoglycoside antibiotics (AGAs) 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 AGAs induce not only single translation errors, but also clusters of errors in full-length proteins in vivo with as much as four amino acid substitutions in a row. The downstream errors in a cluster are much more frequent than the first error (0.4 vs. 10-3, respectively) and independent of the intracellular AGA concentration. The prevalence, length, and composition of error clusters depends not only on the misreading propensity of a given AGA, but also on its ability to inhibit ribosome translocation along the mRNA. Error clusters constitute a new class of misreading events in vivo that may constitute the predominant source of proteotoxic stress at low AGA concentration, which is particularly important for the autocatalytic uptake of the drugs.

INSTRUMENT(S): Q Exactive HF-X, Q Exactive Plus, Q Exactive HF, Q Exactive

ORGANISM(S): Escherichia Coli

SUBMITTER: Ingo Wohlgemuth

LAB HEAD: Marina V Rodnina

PROVIDER: PXD019188 | Pride | 2021-04-06

REPOSITORIES: Pride

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			Action	DRS
	A_gunenc_210519_Tu_insoluble_1to100_ident.raw	Raw
	A_gunenc_210519_Tu_insoluble_1to100_ident_350to500.raw	Raw
	A_gunenc_210519_Tu_insoluble_1to100_ident_650to800.raw	Raw
	A_gunenc_210519_Tu_insoluble_1to100_ident_800to950.raw	Raw
	A_gunenc_210519_Tu_insoluble_1to100_ident_950to1600.raw	Raw

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Translation error clusters induced by aminoglycoside antibiotics.

Wohlgemuth Ingo I Garofalo Raffaella R Samatova Ekaterina E Günenç Aybeg Nafiz AN Lenz Christof C Urlaub Henning H Rodnina Marina V MV

Nature communications 20210323 1

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 erro ...[more]

PMID: 33758186

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