结核病(TB)是由结核分枝杆菌(M.tb)其自然历史可以追溯到70,000年。结核病仍然是全球主要的健康负担。甲基化是一种后复制,转录后和翻译后表观遗传修饰参与转录,翻译,复制,组织特异性表达,胚胎发育,基因组印迹,基因组稳定性和染色质结构,蛋白质蛋白质相互作用和信号转导表明其在病原体如M.tb的存活中不可或缺的作用。病原体利用这种表观遗传机制来产生对某些药物分子的抗性并在致死中存活。抗药性已成为需要应对的重大挑战,也是世卫组织提出的主要关切。甲基转移酶是催化各种底物甲基化的酶。目前的TB靶标都不属于甲基转移酶,其通过研究甲基转移酶作为针对TB的潜在新靶标来提供开发新药物的治疗机会。靶向16SrRNA甲基转移酶同时具有两个目的:a)翻译抑制和b)同时消除其底物甲基化的能力,从而阻止耐药性菌株的出现。存在约40种不同的rRNA甲基转移酶和13种不同的16SrRNA特异性甲基转移酶,它们尚未开发,并为TB的治疗提供了巨大的机会。
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (M.tb) whose natural history traces back to 70,000 years. TB remains a major global health burden. Methylation is a type of post-replication, post-transcriptional and post-translational epi-genetic modification involved in transcription, translation, replication, tissue specific expression, embryonic development, genomic imprinting, genome stability and chromatin structure, protein protein interactions and signal transduction indicating its indispensable role in survival of a pathogen like M.tb. The pathogens use this epigenetic mechanism to develop resistance against certain drug molecules and survive the lethality. Drug resistance has become a major challenge to tackle and also a major concern raised by WHO. Methyltransferases are enzymes that catalyze the methylation of various substrates. None of the current TB targets belong to methyltransferases which provides therapeutic opportunities to develop novel drugs through studying methyltransferases as potential novel targets against TB. Targeting 16S rRNA methyltransferases serves two purposes simultaneously: a) translation inhibition and b) simultaneous elimination of the ability to methylate its substrates hence stopping the emergence of drug resistance strains. There are ~ 40 different rRNA methyltransferases and 13 different 16S rRNA specific methyltransferases which are unexplored and provide a huge opportunity for treatment of TB.