Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis.
Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis.
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DOI：
10.1038/nchembio.539
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发表时间：
2011-04
影响因子：
14.8
通讯作者：
Davis, Benjamin G.
中科院分区：
文献类型：
--
作者：
Backus, Keriann M.;Boshoff, Helena L.;Barry, Conor S.;Boutureira, Omar;Patel, Mitul K.;D'Hooge, Francois;Lee, Seung Seo;Via, Laura E.;Tahlan, Kapil;Barry, Clifton E., III;Davis, Benjamin G.
目前，结核病的检测依赖于不敏感和非特异性的技术；较新的诊断方法理想地会选择特定的细菌过程来提供实时读数。海藻糖转移酶(抗原85A、85B和85C(Ag85A、Ag85B、Ag85C))是结核分枝杆菌细胞膜功能和生物发生的重要介质。通过构建一个系统多样的糖库，我们在这里证明了Ag85酶具有特别广泛的底物专一性。这使得外源添加的合成探针可以专门结合到体外生长的结核分枝杆菌和巨噬细胞中。即使是体积较大的取代基，如含有荧光素的海藻糖探针(FITC-海藻糖)，也会被生长中的细菌结合，从而产生荧光细菌；显微镜下显示了极和膜的选择性标记。将FITC-海藻糖添加到结核杆菌感染的巨噬细胞中，可以选择性、灵敏地检测感染的哺乳动物巨噬细胞中的结核杆菌。这些研究表明，海藻糖的类似物可能被证明是有用的功能探针和其他成像方式。
The detection of tuberculosis currently relies upon insensitive and unspecific techniques; newer diagnostics would ideally co-opt specific bacterial processes to provide real-time readouts. The trehalose mycolyltransesterase enzymes (antigens 85A, 85B and 85C (Ag85A, Ag85B, Ag85C)) serve as essential mediators of cell envelope function and biogenesis in Mycobacterium tuberculosis. Through the construction of a systematically varied sugar library, we show here that Ag85 enzymes have exceptionally broad substrate specificity. This allowed exogenously added synthetic probes to be specifically incorporated into M. tuberculosis growing in vitro and within macrophages. Even bulky substituents, such as a fluorescein-containing trehalose probe (FITC-trehalose), were incorporated by growing bacilli, thereby producing fluorescent bacteria; microscopy revealed selective labeling of poles and membrane. Addition of FITC-trehalose to M. tuberculosis–infected macrophages allowed selective, sensitive detection of M. tuberculosis within infected mammalian macrophages. These studies suggest that analogs of trehalose may prove useful as probes of function and for other imaging modalities.
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DOI：
10.1074/jbc.m809088200
发表时间：
2009-05-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hatzios SK;Schelle MW;Holsclaw CM;Behrens CR;Botyanszki Z;Lin FL;Carlson BL;Kumar P;Leary JA;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
4.5
作者：
Beatty, WL;Rhoades, ER;Russell, DG
通讯作者：
Russell, DG
影响因子：
5.2
作者：
Pratt, MR;Leigh, CD;Bertozzi, CR
通讯作者：
Bertozzi, CR
影响因子：
6.7
作者：
Gobec, Stanislav;Plantan, Ivan;Kikelj, Danijel
通讯作者：
Kikelj, Danijel
影响因子：
4.8
作者：
Murphy, HN;Stewart, GR;Robertson, BD
通讯作者：
Robertson, BD