Bioorthogonal Chemical Reporters for Selective InSitu Probing of Mycomembrane Components in Mycobacteria
Bioorthogonal Chemical Reporters for Selective InSitu Probing of Mycomembrane Components in Mycobacteria
复制标题
DOI：
10.1002/anie.201509216
复制
发表时间：
2016-02-05
影响因子：
16.6
通讯作者：
Swarts, Benjamin M.
中科院分区：
文献类型：
--
作者：
Foley, Hannah N.;Stewart, Jessica A.;Swarts, Benjamin M.
全球病原体结核分枝杆菌和其他种类的棒杆菌亚目具有独特的外膜称为菌膜（MM）。MM由分枝菌酸组成，分枝菌酸与下层阿拉伯半乳聚糖层共价连接或掺入与MM非共价缔合的海藻糖糖脂中。这些结构是通过称为分枝杆菌化的过程产生的，这是分枝杆菌生理学和发病机制的核心，也是结核病药物开发的重要靶点。目前研究分枝菌酰化的方法依赖于在整个细胞背景之外进行的艰苦的分析方法。在此，我们描述了分枝杆菌特异性化学报告，可以选择性地探测活分枝杆菌中的共价阿拉伯半乳聚糖分枝菌酸酯或非共价海藻糖分枝菌酸酯。这些探针，结合生物正交化学，使主要MM组分的选择性原位检测。
The global pathogen Mycobacterium tuberculosis and other species in the suborder Corynebacterineae possess a distinctive outer membrane called the mycomembrane (MM). The MM is composed of mycolic acids, which are either covalently linked to an underlying arabinogalactan layer or incorporated into trehalose glycolipids that associate with the MM non-covalently. These structures are generated through a process called mycolylation, which is central to mycobacterial physiology and pathogenesis and is an important target for tuberculosis drug development. Current approaches to investigating mycolylation rely on arduous analytical methods that occur outside the context of a whole cell. Herein, we describe mycobacteria-specific chemical reporters that can selectively probe either covalent arabinogalactan mycolates or non-covalent trehalose mycolates in live mycobacteria. These probes, in conjunction with bioorthogonal chemistry, enable selective insitu detection of the major MM components.