Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall.
Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall.
复制标题
DOI：
10.1016/j.tcsw.2020.100044
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Besra GS
中科院分区：
文献类型：
--
作者：
Batt SM;Burke CE;Moorey AR;Besra GS
结核分枝杆菌是导致结核病的细菌，是全球主要的传染性病原体死亡原因。这种成功部分依赖于独特的细胞壁，它由一层厚厚的蜡质外壳和紧密堆积的复合糖，脂质和肽层组成。这种涂层为抗生素和宿主的防御提供了一个保护性的疏水屏障，同时使细菌能够通过痰液有效传播，感染新宿主的巨噬细胞并在其中存活。然而，这一成功的一部分是有代价的，目前许多一线和二线药物靶向参与细胞壁生物合成的酶。这枚硬币的另一面是，对这些药物的耐药性在靶酶或药物的活化途径中发展，为新的耐药临床菌株铺平了道路。这篇综述提供了一个概要的结构和合成的细胞壁和目前的主要药物和目标，沿着任何耐药机制。
Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, is the global leading cause of mortality from an infectious agent. Part of this success relies on the unique cell wall, which consists of a thick waxy coat with tightly packed layers of complexed sugars, lipids and peptides. This coat provides a protective hydrophobic barrier to antibiotics and the host’s defences, while enabling the bacterium to spread efficiently through sputum to infect and survive within the macrophages of new hosts. However, part of this success comes at a cost, with many of the current first- and second-line drugs targeting the enzymes involved in cell wall biosynthesis. The flip side of this coin is that resistance to these drugs develops either in the target enzymes or the activation pathways of the drugs, paving the way for new resistant clinical strains. This review provides a synopsis of the structure and synthesis of the cell wall and the major current drugs and targets, along with any mechanisms of resistance.