Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, is currently resistant to antibiotics and has undergone transcriptional adaptation to them, yet only a few transcription factors regulating mycobacterial drug resistance have been identified. In this study, the transcriptional regulatory protein Rv2250c of the TetR family was found to be a regulatory molecule of INH. Compared with wild-type strains, strains lacking the rv2250c gene showed higher minimum inhibitory concentrations (MICs) and greater intracellular survival in macrophages under INH stress. Furthermore, the INH competition with Rv2250c weakens its interaction with the efflux pump gene rv3728, thereby reducing its negative regulatory effect. This enhances the function of the MTB cell wall efflux pump, reducing the accumulation of ethidium bromide (EtBr) within the bacteria. In summary, we found that Rv2250c can regulate INH susceptibility by modulating the expression of efflux pump-encoding genes.

Keywords: Mycobacterium tuberculosis; Efflux pump Rv3728; Isoniazid; Transcriptional regulatory protein Rv2250c.