CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Biosciences PhD Program, Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
Microbiology (Reading). 2014 Aug;160(Pt 8):1547-1570. doi: 10.1099/mic.0.075895-0. Epub 2014 May 23.
Trehalose is a natural glucose disaccharide identified in the 19th century in fungi and insect cocoons, and later across the three domains of life. In members of the genus Mycobacterium, which includes the tuberculosis (TB) pathogen and over 160 species of nontuberculous mycobacteria (NTM), many of which are opportunistic pathogens, trehalose has been an important focus of research over the last 60 years. It is a crucial player in the assembly and architecture of the remarkable mycobacterial cell envelope as an element of unique highly antigenic glycolipids, namely trehalose dimycolate ('cord factor'). Free trehalose has been detected in the mycobacterial cytoplasm and occasionally in oligosaccharides with unknown function. TB and NTM infection statistics and death toll, the decline in immune responses in the aging population, human immunodeficiency virus/AIDS or other debilitating conditions, and the proliferation of strains with different levels of resistance to the dated drugs in use, all merge into a serious public-health threat urging more effective vaccines, efficient diagnostic tools and new drugs. This review deals with the latest findings on mycobacterial trehalose biosynthesis, catabolism, processing and recycling, as well with the ongoing quest for novel trehalose-related mechanisms to be targeted by novel TB therapeutics. In this context, the drug-discovery pipeline has recently included new lead compounds directed toward trehalose-related targets highlighting the potential of these pathways to stem the tide of rising drug resistance.
海藻糖是一种天然葡萄糖二糖，于 19 世纪在真菌和昆虫茧中被发现，后来在生命的三个领域中都有发现。在分枝杆菌属的成员中，包括结核分枝杆菌（TB）病原体和超过 160 种非结核分枝杆菌（NTM），其中许多是机会性病原体，海藻糖一直是过去 60 年来研究的重要焦点。作为独特高度抗原性糖脂的一个组成部分，海藻糖是组装和构建非凡分枝杆菌细胞包膜的关键因素，即海藻糖二分枝酸酯（“索状因子”）。游离海藻糖已在分枝杆菌细胞质中检测到，偶尔在具有未知功能的寡糖中检测到。结核分枝杆菌和非结核分枝杆菌感染的统计数据和死亡人数、老龄化人口免疫反应的下降、人类免疫缺陷病毒/艾滋病或其他使人衰弱的疾病，以及对现有药物耐药程度不同的菌株的增殖，所有这些都合并成了一个严重的公共卫生威胁，促使人们开发更有效的疫苗、有效的诊断工具和新药。这篇综述涉及分枝杆菌海藻糖生物合成、分解代谢、加工和再循环的最新发现，以及正在探索新的与海藻糖相关的机制，以作为新型结核分枝杆菌治疗的靶点。在这种情况下，药物发现管道最近包括了针对与海藻糖相关的靶点的新先导化合物，突出了这些途径在遏制耐药性上升方面的潜力。
