title: Antibiotic-induced ribosomal assembly defects result from changes in the synthesis of ribosomal proteins.
abstract: Inhibitors of protein synthesis cause defects in the assembly of ribosomal subunits. In response to treatment with the antibiotics erythromycin or chloramphenicol, precursors of both large and small ribosomal subunits accumulate. We have used a pulse-labelling approach to demonstrate that the accumulating subribosomal particles maturate into functional 70S ribosomes. The protein content of the precursor particles is heterogeneous and does not correspond with known assembly intermediates. Mass spectrometry indicates that production of ribosomal proteins in the presence of the antibiotics correlates with the amounts of the individual ribosomal proteins within the precursor particles. Thus, treatment of cells with chloramphenicol or erythromycin leads to an unbalanced synthesis of ribosomal proteins, providing the explanation for formation of assembly-defective particles. The operons for ribosomal proteins show a characteristic pattern of antibiotic inhibition where synthesis of the first proteins is inhibited weakly but gradually increases for the subsequent proteins in the operon. This phenomenon most likely reflects translational coupling and allows us to identify other putative coupled non-ribosomal operons in the Escherichia coli chromosome.
authors.affiliation: Institutes of Molecular and Cell Biology Technology, University of Tartu, Tartu, Estonia.
authors.forename: Triinu
authors.initials: T
authors.lastname: Siibak
authors.forename: Lauri
authors.initials: L
authors.lastname: Peil
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dönhöfer
authors.forename: Age
authors.initials: A
authors.lastname: Tats
authors.forename: Maido
authors.initials: M
authors.lastname: Remm
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Wilson
authors.forename: Tanel
authors.initials: T
authors.lastname: Tenson
authors.forename: Jaanus
authors.initials: J
authors.lastname: Remme
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D054657:Ribosome Subunits / Q000187:drug effects / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D012269:Ribosomal Proteins; D004917:Erythromycin; D002701:Chloramphenicol