Transcription Factor Rv1453 Contributes to Multidrug Sensitivity of Mycobacterium tuberculosis: A Potential Role for Lipid Metabolism

The growing prevalence of multidrug-resistant Mycobacterium tuberculosis complicates tuberculosis control efforts. We discovered that Rv1453, as a new transcription factor, is crucial for lipid metabolism in bacteria. Rv1453 suppresses expression of genes related to fatty acid β-oxidation (fadD18, fadE5, fadE12, fadE13, fadE18, fadE30, fadE31, echA7) and genes for lipid synthesis (accA2, accD2). Furthermore, acyl-Coenzyme A influences signals regulated by Rv1453. Removing Rv1453 boosts expression of these genes, alters cell wall lipid composition, changes colony morphology, thickens the cell wall, and contributes to the reduced multidrug susceptibility. These findings point to an association between Rv1453-mediated lipid metabolism and multidrug sensitivity in Mycobacterium tuberculosis.