Muralikrishnan Balaji, Edison Lekshmi K, Dusthackeer Azger, Jijimole G R, Ramachandran Ranjit, Madhavan Aravind, Kumar Ramakrishnan Ajay
Mycobacterium Research Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India.
J Antibiot (Tokyo). 2022 Apr;75(4):226-235. doi: 10.1038/s41429-022-00503-z. Epub 2022 Feb 8.
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.
新型抗结核药物对于治疗由结核分枝杆菌引起的耐药结核病至关重要。我们最近报道了金霉素A在体外和感染巨噬细胞中的抗分枝杆菌活性。在本研究中，我们报告它能抑制耐药结核分枝杆菌临床菌株的生长，并与乙胺丁醇、环丙沙星和新生霉素等抗结核药物协同作用。在探索其作用机制时，发现金霉素A具有杀菌作用，通过与特定序列的DNA相互作用并抑制结核分枝杆菌的拓扑异构酶I活性来发挥这种活性。它对该病原体的DNA促旋酶也表现出微弱的抑制作用。
