indolmycin and chuangxinmycin

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.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Chromatography, Liquid; Drug Resistance, Multiple, Bacterial; Indoles; Isoenzymes; Mass Spectrometry; Microbial Sensitivity Tests; Molecular Sequence Data; Mutagenesis, Site-Directed; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Streptomyces; Streptomyces coelicolor; Streptomyces griseus; Tryptophan; Tryptophan-tRNA Ligase

Streptomyces coelicolor has two genes encoding tryptophanyl-tRNA synthetases, one of which (trpRS1) is resistant to and transcriptionally activated by indolmycin. We found that this gene also confers resistance to chuangxinmycin (another antibiotic that inhibits bacterial tryptophanyl-tRNA synthetases) and that its transcription is not absolutely dependent on either antibiotic.

Topics: Amino Acyl-tRNA Synthetases; Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Indoles; Molecular Sequence Data; Streptomyces coelicolor; Transcription Initiation Site