Abstract: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M. tb) and mainly spread by airborne transmission, remains a global health problem. After the wide clinical utilization of antibiotics in treatment of TB, the drug resistance has become a major threat to global TB control and this threat has been heightened by the emergence and propagation of multi-drug resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and totally drug-resistant tuberculosis (TDR-TB). The research in the mode-of-action mechanisms of anti-TB drugs and the drug resistance mechanisms of M. tb will facilitate the novel anti-TB drugs development, the optimization of current anti-TB drugs and the development of new drug resistance diagnosis technologies. This review provides a comprehensive overview of mode-of-action mechanisms of new anti-TB drugs and mechanisms of resistance to these drugs in M. tb, with particular attention to the role of newly-identified mycobacterial outer-membrane channel proteins (PE/PPE proteins) in TB drug resistance.

Key words: Mycobacterium tuberculosis, drug mode-of-action, resistance mechanism, outer-membrane channel proteins, PE/PPE proteins