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Metformin and Rifampicin combination augments active to latent tuberculosis conversion: A computational study
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2020-10-15 , DOI: 10.1002/bab.2052 Deepak Yadav 1 , Sumanpreet Kaur 1 , Dibyajyoti Banerjee 1 , Rajasri Bhattacharyya 1
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2020-10-15 , DOI: 10.1002/bab.2052 Deepak Yadav 1 , Sumanpreet Kaur 1 , Dibyajyoti Banerjee 1 , Rajasri Bhattacharyya 1
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Tuberculosis, a global threat, is a highly infectious disease intensified by the emergence of drug-resistant strains. In tuberculosis disease spectrum, a typical situation is a dormant or latent phase where a person exposed to Mycobacterium tuberculosis has the reservoir of the disease that may or may not result in an active state. Existence of the dormant state is retarding the eradication of tuberculosis. Transcription of several genes helps M. tuberculosis to survive in nonreplicative mode. DosR transcription factor is the hallmark for this genesis. Diabetes mellitus is a predisposition factor leading to the development of tuberculosis and latent tuberculosis. High plasma insulin concentrations in the prediabetic state can increase the tuberculosis bacterium. On the other hand, antidiabetic drug metformin is known to reduce active tuberculosis disease when provided in combination with antitubercular therapy. However, the effect of the same on latent tuberculosis is still unknown. In the present work using tools of computational biology, we have tried to find the consequence of adding metformin in combination with rifampicin, a well-known antitubercular drug, on molecular mechanisms of latent tuberculosis. We have investigated whether metformin and rifampicin interact with DosR machinery or not. Our results indicate that if metformin-bound DosR–DNA complex binds with rifampicin, it will result in the conversion of active tuberculosis to latent tuberculosis.
中文翻译：
二甲双胍和利福平联合使用可增强活性至潜伏性结核病的转化：一项计算研究
结核病是一种全球性威胁，是一种高度传染性疾病，因耐药菌株的出现而加剧。在结核病谱中，典型的情况是处于休眠或潜伏期，其中暴露于结核分枝杆菌的人具有可能会或可能不会导致活跃状态的疾病宿主。休眠状态的存在阻碍了结核病的根除。几个基因的转录有助于结核分枝杆菌在非复制模式下生存。DosR 转录因子是这一起源的标志。糖尿病是导致结核病和潜伏性结核病发展的易感因素。糖尿病前期状态的高血浆胰岛素浓度可增加结核菌。另一方面，已知抗糖尿病药物二甲双胍与抗结核治疗联合使用可减少活动性结核病。然而，它对潜伏性结核病的影响仍然未知。在目前使用计算生物学工具的工作中，我们试图找出将二甲双胍与利福平（一种著名的抗结核药物）联合使用对潜伏性结核病分子机制的影响。我们研究了二甲双胍和利福平是否与 DosR 机制相互作用。
更新日期：2020-10-15
中文翻译：
二甲双胍和利福平联合使用可增强活性至潜伏性结核病的转化：一项计算研究
结核病是一种全球性威胁，是一种高度传染性疾病，因耐药菌株的出现而加剧。在结核病谱中，典型的情况是处于休眠或潜伏期，其中暴露于结核分枝杆菌的人具有可能会或可能不会导致活跃状态的疾病宿主。休眠状态的存在阻碍了结核病的根除。几个基因的转录有助于结核分枝杆菌在非复制模式下生存。DosR 转录因子是这一起源的标志。糖尿病是导致结核病和潜伏性结核病发展的易感因素。糖尿病前期状态的高血浆胰岛素浓度可增加结核菌。另一方面，已知抗糖尿病药物二甲双胍与抗结核治疗联合使用可减少活动性结核病。然而，它对潜伏性结核病的影响仍然未知。在目前使用计算生物学工具的工作中，我们试图找出将二甲双胍与利福平（一种著名的抗结核药物）联合使用对潜伏性结核病分子机制的影响。我们研究了二甲双胍和利福平是否与 DosR 机制相互作用。
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