Chrysomycin A inhibits the topoisomerase I of Mycobacterium tuberculosis

Abstract

AbstractNovel anti-tuberculosis drugs are essential to manage drug resistant tuberculosis, caused by the notorious pathogen Mycobacterium tuberculosis. We recently reported the antimycobacterial activity of chrysomycin A in vitro and in infected macrophages. In this study, we report that the molecule inhibits the growth of drug resistant clinical strains of Mycobacterium tuberculosis and acts in synergy with anti-TB drugs such as ethambutol, ciprofloxacin and novobiocin. In pursuit of its mechanism of action, it was found that chrysomycin A renders bactericidal activity by interacting with DNA at specific sequences and by inhibiting topoisomerase I activity of Mycobacterium tuberculosis. It also exhibits weak inhibition of gyrase enzyme of the pathogen.