GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE267nnn/GSE267532/primaryOK200TranscriptomicsMycobacterium tuberculosisExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE267532GEOGSEfalseChemically Induced Alanine Auxotrophy of Mycobacterium tuberculosisUtilizing 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.2026/09/24GSE267532GSM8268363GSM8268362GSM8268361GSM826836434478267532Mycobacterium tuberculosis[42466413]