Chrysomycin A inhibits the topoisomerase I of Mycobacterium tuberculosis
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Balaji Muralikrishnan1, Lekshmi K Edison1, Azger Dusthackeer2
1Mycobacterium Research Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
Abstract:
Novel anti-tuberculosis drugs are essential to manage drug-resistant tuberculosis, caused by Mycobacterium tuberculosis. We recently reported the antimycobacterial activity of chrysomycin A in vitro and in infected macrophages. In this study, we report that it inhibits the growth of drug-resistant clinical strains of M. 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 is bactericidal and exerts this activity by interacting with DNA at specific sequences and by inhibiting the topoisomerase I activity of M. tuberculosis. It also exhibits weak inhibition of the DNA gyrase enzyme of the pathogen.
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