Research ArticleDrug Discovery

High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds

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Science Translational Medicine  21 Feb 2018:
Vol. 10, Issue 429, eaal3973
DOI: 10.1126/scitranslmed.aal3973

Boosting the antibiotics pipeline

Antibiotic discovery requires innovative phenotypic assays to identify the mode of action of compounds during large-scale drug screening. Now, Zampieri et al. have developed a high-throughput method to systematically quantify and interpret dynamic metabolome responses of mycobacteria to new antimicrobial compounds. They demonstrate how one can infer the mode of action of uncharacterized antimycobacterial compounds by comparing drug-induced metabolic responses in Mycobacterium smegmatis. Their combined mass spectrometry–based metabolomics and computational workflow scaled with the size of typical compound libraries and hence could facilitate the selection of antimicrobial compound leads with potentially new modes of action.

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