Indolmycin

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Background

IC50: 30 μM for prokaryotic tryptophanyl-tRNA synthetase Indolmycin is an antibiotic. Tryptophanyl-tRNA synthetase (TrpRS) catalyzes activation of tryptophan through ATP and transfer to tRNATrp , leading to translation of the genetic code for tryptophan.In vitro: Indolmycin was found to ba a bacteriostatic that showed good activity against methicillin-resistant S. aureus, methicillin-susceptible Staphylococcus aureus, and vancomycin-intermediate S. aureus, including strains resistant to mupirocin or fusidic acid. Spontaneous indolmycin-resistant mutants was observed at a lower frequency than those selected by mupirocin or fusidic acid and exhibited no cross-resistance with the comparative drugs. High-level resistance of indolmycin at its MIC of 128 mg/L that was associated with an H43N mutation in tryptophanyl-tRNA synthetase, the target enzyme of indolmycin, led to loss of bacterial fitness. However, the locus responsible for low-level indolmycin resistance (indolmycin MICs 8-32 mg/L) was not identified [1].In vivo: Animal study found that indolmycin could completely clear H. pylori in experimentally infected Mongolian gerbils at a dose of 10 mg/kg. Therefore, indolmycin could be regarded as a candidate for the treatment of H. pylori infection [2].Clinical trial: So far, no clinical study has been conducted.

[1] Hurdle JG, O'Neill AJ, Chopra I. Anti-staphylococcal activity of indolmycin, a potential topical agent for control of staphylococcal infections. J Antimicrob Chemother. 2004 Aug;54(2):549-52. Epub 2004 Jul 8.
[2] Vecchione JJ, Sello JK. A novel tryptophanyl-tRNA synthetase gene confers high-level resistance to indolmycin. Antimicrob Agents Chemother 2009; 53: 3972-3980.