Engineered E. coli That Detect and Respond to Gut Inflammation through Nitric Oxide Sensing
Engineered E. coli That Detect and Respond to Gut Inflammation through Nitric Oxide Sensing
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DOI：
10.1021/sb3000595
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发表时间：
2012-10-01
影响因子：
4.7
通讯作者：
Sueel, Guerol M.
中科院分区：
文献类型：
--
作者：
Archer, Eric J.;Robinson, Andra B.;Sueel, Guerol M.
合成生物学的进步现在允许微生物重新编程以执行特定的任务。在这里，我们描述了一种能够感知和响应哺乳动物炎症信号存在的工程化大肠杆菌菌株的开发。合成的基因调控电路被设计成永久性地改变基因的表达，以响应具有良好特征的炎症信号-一氧化氮。一氧化氮的检测启动了DNA重组酶的表达，导致DNA开关的永久激活。我们证明，含有这种合成电路的大肠杆菌对来自化学和生物来源的一氧化氮做出反应，在一氧化氮供体化合物或发炎的小鼠回肠外植体存在的情况下，发生永久性的DNA重组。未来，这种合成的遗传电路将得到优化，使大肠杆菌能够可靠地检测到体内的炎症并做出反应。
Advances in synthetic biology now allow for the reprogramming of microorganisms to execute specific tasks. Here, we describe the development of an engineered strain of E. coli capable of sensing and responding to the presence of a mammalian inflammatory signal. The synthetic gene regulatory circuit is designed to permanently alter gene expression in response to the well characterized inflammatory signal, nitric oxide. The detection of nitric oxide initiates the expression of a DNA recombinase, causing the permanent activation of a DNA switch. We demonstrate that E. coli containing this synthetic circuit respond to nitric oxide from both chemical and biological sources, with permanent DNA recombination occurring in the presence of nitric oxide donor compounds or inflamed mouse ileum explants. In the future, this synthetic genetic circuit will be optimized to allow E. coli to reliably detect and respond to inflammation in vivo.