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Chemically Induced Alanine Auxotrophy of Mycobacterium tuberculosis

ABSTRACT: Utilizing a novel computational chemogenomics method to discover new antitubercular compounds, a hit compound designated TI-374 was identified with a minimal inhibitory concentration of 540 nM against M. tuberculosis H37Rv. To investigate the mechanism of action, transcriptional profiling of treated cultures was conducted by RNA-seq. Combined with computational chemogenomic target prediction, metabolomic analysis of treated cultures, nutritional suppression experiments, activity in biochemical assays against purified protein, and whole-genome sequencing of resistant mutants, this transcriptomic data is consistent with a novel mechanism of action whereby TI-374 inhibits the alanine aminotransferase annotated as aspC. This activity interferes with alanine biosynthesis, which is required for growth of the pathogen.

ORGANISM(S): Mycobacterium tuberculosis

PROVIDER: GSE267532 | GEO | 2026/09/24

REPOSITORIES: GEO

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