Assistant Professor, Department of Pharmaceutical Chemistry, Dr L H Hiranandani College of Pharmacy, Ulhasnagar, Maharashtra, India.
Indian J Pharmacol. 2022 Sep-Oct;54(5):353-363. doi: 10.4103/ijp.IJP_667_20.
Mycobacterium tuberculosis (MTB) requires a perpetual supply of iron for its sustenance. Iron scarcity and its limited availability in the host environment because of an encounter of various sites during the establishment of infection has led to the evolution of strategies for iron uptake, which includes biosynthesis of iron-chelating molecules called siderophores, Heme uptake pathways, recently discovered host iron transport protein receptors like glyceraldehyde-3-phosphate dehydrogenase and the development of machinery for proper storage of the acquired iron and its regulation. The components of the iron uptake machineries are viable targets in multidrug-resistant tuberculosis, some of which include the MmpL3 heme transfer protein, MbtA enzyme, and the ESX-3 system, while employment of approaches like the synthesis of siderophore drug conjugates, heme analogs, xenosiderophores as drug delivery agents, and the blockade of siderophore recycling are encouraged too. Thus, the mentioned discoveries stand as promising targets against various strains of MTB.
结核分枝杆菌（MTB）需要持续供应铁才能生存。由于在感染建立过程中会遇到各种部位，导致铁的稀缺和宿主环境中铁的有限可用性，因此出现了铁摄取策略的进化，包括合成铁螯合分子，称为 siderophores、血红素摄取途径，最近发现宿主铁转运蛋白受体，如甘油醛-3-磷酸脱氢酶和用于适当储存获得的铁及其调节的机制的发展。铁摄取机制的成分是耐多药结核分枝杆菌的可行靶点，其中一些包括 MmpL3 血红素转移蛋白、MbtA 酶和 ESX-3 系统，同时鼓励采用合成 siderophore 药物缀合物、血红素类似物、外源性 siderophores 作为药物递送剂以及阻断 siderophore 再循环等方法。因此，这些发现为针对各种结核分枝杆菌菌株提供了有希望的靶点。
