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bioRxiv · 10.1101/2021.06.23.449690

Chrysomycin A inhibits the topoisomerase I of Mycobacterium tuberculosis.

Muralikrishnan, B.·Edison, L. K.·Dusthackeer, A.·Reji, J. G.·Ramachandran, R.·Madhavan, A.·Ajay Kumar, R.
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Abstract

Novel 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.

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Muralikrishnan, B., Edison, L. K., Dusthackeer, A., Reji, J. G., Ramachandran, R., Madhavan, A., Ajay Kumar, R.. 2021-06-24. Chrysomycin A inhibits the topoisomerase I of Mycobacterium tuberculosis.. https://doi.org/10.1101/2021.06.23.449690

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