Implications of Mycobacterium tuberculosis Metabolic Adaptability on Drug Discovery and Development
Implications of Mycobacterium tuberculosis Metabolic Adaptability on Drug Discovery and Development
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DOI：
10.1021/acsinfecdis.1c00627
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发表时间：
2022-03-11
影响因子：
5.3
通讯作者：
Singh, Vinayak
中科院分区：
文献类型：
--
作者：
Cardoso, Nicole C.;Chibale, Kelly;Singh, Vinayak
结核病仍然是一个全球性的健康威胁，由于耐药结核分枝杆菌感染的增加，这种威胁正在加剧。为了解决这个问题，药物发现计划激增，以开发新的，有效的化合物，并确定病原体中有希望的药物靶点。M.结核病生物学已经成为潜在的新型药物靶点的丰富来源，是细胞壁生物合成和能量代谢。这两个过程对M.复制和非复制条件下的结核病。然而，这两种方法在不同的条件下也具有内在的适应性。此外，细胞壁生物合成是能量密集型的，因此依赖于有效运作的能量生产系统。这一观点的重点是细胞壁的生物合成和能量代谢之间的相互作用，在M。结核病，一种途径的适应如何影响另一种途径，以及这对药物发现和开发以及新药物靶点的鉴定可能产生的后果。
Tuberculosis remains a global health threat that is being exacerbated by the increase in infections attributed to drug resistant Mycobacterium tuberculosis. To combat this, there has been a surge in drug discovery programs to develop new, potent compounds and identify promising drug targets in the pathogen. Two areas of M. tuberculosis biology that have emerged as rich sources of potential novel drug targets are cell wall biosynthesis and energy metabolism. Both processes are important for survival of M. tuberculosis under replicating and nonreplicating conditions. However, both processes are also inherently adaptable under different conditions. Furthermore, cell wall biosynthesis is energy intensive and, thus, reliant on an efficiently functioning energy production system. This Perspective focuses on the interplay between cell wall biosynthesis and energy metabolism in M. tuberculosis, how adaptations in one pathway may affect the other, and what consequences this could have for drug discovery and development and the identification of novel drug targets.