Mistranslation induced by streptomycin provokes a RecABC/RuvABC-dependent mutator phenotype in Escherichia coli cells.
Translational stress-induced mutagenesis (TSM) refers to the mutator phenotype observed in Escherichia coli cells expressing a mutant allele (mutA or mutC) of the glycine tRNA gene glyV (or glyW). Because of an anticodon mutation, expression of the mutA allele results in low levels of Asp-->Gly mistranslation. The mutA phenotype does not require lexA-regulated SOS mutagenesis functions, and appears to be suppressed in cells defective for RecABC-dependent homologous recombination functions. To test the hypothesis that the TSM response is mediated by non-specific mistranslation rather than specific Asp-->Gly misreading, we asked if streptomycin (Str), an aminoglycoside antibiotic known to promote mistranslation, can provoke a mutator phenotype. We report that Str induces a strong mutator phenotype in cells bearing certain alleles of rpsL, the gene encoding S12, an essential component of the ribosomal 30 S subunit. The phenotype is strikingly similar to that observed in mutA cells in its mutational specificity, as well as in its requirement for RecABC-mediated homologous recombination functions. Expression of Str-inducible mutator phenotype correlates with mistranslation efficiency in response to Str. Thus, mistranslation in general is able to induce the TSM response. The Str-inducible mutator phenotype described here defines a new functional class of rpsL alleles, and raises interesting questions on the mechanism of action of Str, and on bacterial response to antibiotic stress.
Balashov
Sergey
S
Department of Microbiology and Molecular Genetics, UMDNJ - New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Humayun
M Zafri
MZ
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018389:Codon, Nonsense / Q000235:genetics; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005787:Gene Frequency; D007763:Lac Operon / Q000235:genetics; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics; D010641:Phenotype; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011938:Rec A Recombinases / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D018085:Regulon / Q000235:genetics; D000091243:Ribosomal Protein S9; D013014:SOS Response, Genetics / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics; D013307:Streptomycin / Q000494:pharmacology*; D013489:Suppression, Genetic / Q000235:genetics; D000099160:LexA Repressor Protein
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018389:Codon, Nonsense; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D029968:Escherichia coli Proteins; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases; D011500:Protein Synthesis Inhibitors; D011938:Rec A Recombinases; D000091243:Ribosomal Protein S9; D012697:Serine Endopeptidases; D013307:Streptomycin; D000099160:LexA Repressor Protein; C000717190:RpsI protein, E coli; C061260:RuvB protein, Bacteria; C069806:ruvC protein, E coli; C071059:Holliday junction DNA helicase, E coli