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Illuminating vital surface molecules of symbionts in health and disease.
Nature Microbiology ( IF 20.5 ) Pub Date : 2017-Jun-26 , DOI: 10.1038/nmicrobiol.2017.99
Jason E. Hudak , David Alvarez , Ashwin Skelly , Ulrich H. von Andrian , Dennis L. Kasper

The immunomodulatory surface molecules of commensal and pathogenic bacteria are critical to microorganisms' survival and the host's response1,2. Recent studies have highlighted the unique and important responses elicited by commensal-derived surface macromolecules3-5. However, the technology available to track these molecules in host cells and tissues remains primitive. We report, here, an interdisciplinary approach that uses metabolic labelling combined with bioorthogonal click chemistry (that is, reactions performed in living organisms)6 to specifically tag up to three prominent surface immunomodulatory macromolecules-peptidoglycan, lipopolysaccharide and capsular polysaccharide-either simultaneously or individually in live anaerobic commensal bacteria. Importantly, the peptidoglycan labelling enables, for the first time, the specific labelling of live endogenous, anaerobic bacteria within the mammalian host. This approach has allowed us to image and track the path of labelled surface molecules from live, luminal bacteria into specific intestinal immune cells in the living murine host during health and disease. The chemical labelling of three specific macromolecules within a live organism offers the potential for in-depth visualization of host-pathogen interactions.

中文翻译:

在健康和疾病中照亮共生体的重要表面分子。

共生和致病菌的免疫调节表面分子对于微生物的存活和宿主的反应1,2至关重要。最近的研究强调了由共生衍生的表面大分子3-5引起的独特而重要的反应。然而,可用于追踪宿主细胞和组织中这些分子的技术仍然是原始的。我们在这里报告了一种跨学科的方法,该方法将代谢标记与生物正交点击化学(即在活生物体中发生的反应)结合起来使用6在活厌氧共生细菌中同时或分别特异性标记多达三个突出的表面免疫调节大分子肽聚糖,脂多糖和荚膜多糖。重要的是,肽聚糖标记首次实现了哺乳动物宿主内活的内源性厌氧细菌的特异性标记。这种方法使我们能够在健康和疾病期间成像并跟踪标记的表面分子从活的腔细菌进入活的鼠宿主中特定的肠道免疫细胞的路径。活生物体中三个特定大分子的化学标记为深入可视化宿主-病原体相互作用提供了潜力。
更新日期:2017-06-27
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