HTH-type transcriptional regulator EtbR (EtbR) (EtbR)

EtbR (Rv0273c) is a member of the TetR family of transcriptional regulators in Mycobacterium tuberculosis that serves as a critical molecular link in the synergistic interaction between the first-line antitubercular drugs ethambutol and isoniazid. It functions as a transcriptional repressor by specifically binding to the promoter region of the inhA gene, which encodes the enoyl-acyl carrier protein reductase essential for mycolic acid biosynthesis and is the primary target of isoniazid. Research has demonstrated that ethambutol directly binds to EtbR, acting as a ligand that enhances the regulator's affinity for the inhA promoter, thereby further suppressing inhA expression and reducing the levels of the InhA enzyme. This molecular mechanism effectively sensitizes the bacterium to isoniazid, explaining the long-observed clinical synergy between these two drugs and identifying EtbR as a potential target for the development of novel adjuvants to enhance tuberculosis treatment efficacy.

Other names

Rv0273cEthambutol-responsive regulatorHTH-type transcriptional regulator Rv0273c

Ethambutol acts as a ligand for EtbR, increasing its DNA-binding affinity for the inhA promoter and enhancing transcriptional repression of the inhA gene, which reduces InhA enzyme levels and sensitizes the bacterium to isoniazid.