A novel tryptophanyl-tRNA synthetase gene confers high-level resistance to indolmycin.
Indolmycin, a potential antibacterial drug, competitively inhibits bacterial tryptophanyl-tRNA synthetases. An effort to identify indolmycin resistance genes led to the discovery of a gene encoding an indolmycin-resistant isoform of tryptophanyl-tRNA synthetase. Overexpression of this gene in an indolmycin-sensitive strain increased the indolmycin MIC 60-fold. Its transcription and distribution in various bacterial genera were assessed. The level of resistance conferred by this gene was compared to that of a known indolmycin resistance gene and to those of genes with resistance-conferring point mutations.
Vecchione
James J
JJ
Department of Chemistry, Brown University, 324 Brook St., Providence, RI 02912, USA.
Sello
Jason K
JK
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002853:Chromatography, Liquid; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D013305:Streptomyces griseus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D014364:Tryptophan / Q000494:pharmacology; D014369:Tryptophan-tRNA Ligase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D000900:Anti-Bacterial Agents; D007211:Indoles; D007527:Isoenzymes; C014414:chuangxinmycin; D014364:Tryptophan; D014369:Tryptophan-tRNA Ligase; C001447:indolmycin