Nunes-Costa Daniela, Maranha Ana, Costa Mafalda, Alarico Susana, Empadinhas Nuno
CNC - Center for Neuroscience and Cell Biology, Molecular Mycobacteriology Group, Faculty of Medicine, Campus I, University of Coimbra, 3004-504 Coimbra, Portugal.
Glycobiology. 2017 Mar 4;27(3):213-227. doi: 10.1093/glycob/cww132.
Despite the progressive decline in tuberculosis mortality, strains resistant to our dated antibiotics remain a global threat, as are the emerging nontuberculous mycobacteria, ubiquitous in natural and human environments. This pressing situation boosted by debilitated immune systems, chronic illness and the aged population calls for efficient strategies to fight these successful organisms, and identifying pathways critical for their survival is a crucial step towards this goal. In this context, the glycoside glucosylglycerate (GG) has been implicated in the adaptation of mycobacteria to nitrogen starvation and to thermal stress, and the key gene for GG synthesis has been considered essential for Mycobacterium tuberculosis growth. The many organisms we now know to have genes for GG metabolism opened new exciting avenues of research into its functions, hinting for example at hypothetical roles as an inter-cellular messenger among bacteria and in microbe-plant interactions, or at key roles in the global nitrogen cycle beyond what cyanobacteria and mycobacteria have taught us so far. Indeed, the insights into GG biology gained over the last decade have changed the perception of GG from a rare polysaccharide constituent to a widespread molecule with multiple functions and biosynthetic origins. It is now possible to build upon this knowledge and further explore its physiological importance in both pathogenic and environmentally relevant microorganisms. In particular, the vital roles of GG and of its important derivative the mycobacterial methylglucose lipopolysaccharide (MGLP) discussed here are now evident, making their metabolic links attractive targets for the development of new urgently needed antimycobacterial therapies.
尽管结核病死亡率在逐步下降，但对我们现有的抗生素耐药的菌株仍然是全球威胁，新出现的非结核分枝杆菌也是如此，它们在自然和人类环境中无处不在。免疫系统衰弱、慢性病和老年人口加剧了这种紧迫形势，这就需要有效的策略来对抗这些成功存活的病原体，而确定对它们的生存至关重要的途径是朝着这一目标迈出的关键一步。在这种背景下，糖苷葡糖甘油酸（GG）与分枝杆菌适应氮饥饿和热应激有关，并且GG合成的关键基因被认为对结核分枝杆菌的生长至关重要。我们现在知道许多生物体都有GG代谢基因，这为其功能的研究开辟了新的、令人兴奋的途径，例如暗示其在细菌间作为细胞间信使以及在微生物与植物相互作用中的假设作用，或者在全球氮循环中发挥关键作用，而这超出了目前蓝细菌和分枝杆菌所揭示的范围。事实上，过去十年对GG生物学的深入了解已经改变了人们对GG的看法，从一种罕见的多糖成分转变为一种具有多种功能和生物合成起源的广泛存在的分子。现在可以基于这些知识进一步探索其在致病微生物和与环境相关的微生物中的生理重要性。特别是，本文讨论的GG及其重要衍生物分枝杆菌甲基葡萄糖脂多糖（MGLP）的重要作用现在已经很明显，这使得它们的代谢联系成为开发急需的新型抗分枝杆菌疗法的有吸引力的靶点。
