A Household Yeast Biosensor for Cholera

 描述(申请人提供)：腹泻疾病是发展中国家十大死亡原因之一，霍乱弧菌是主要细菌病原体之一，每年感染约400万人，导致约12万人死亡。尽管霍乱是一种容易治疗的疾病，但它继续造成致命的流行病，因为在实践中，临床检测很少发生在偏远医院之外，供水中的环境检测仍然具有挑战性。最先进的霍乱诊断方法是用于试纸试验的纯化抗体；不幸的是，试纸试验昂贵得令人望而却步，而且不能直接在霍乱流行的地方社区使用。将需要一种新的变革性的检测模式，以产生一个极其廉价和可广泛分布的系统，用于对霍乱的持续当地监测。我们试图克服目前本地诊断的障碍，利用现有的合成生物学成分来制作一种新的廉价和简单的诊断方法，建立在冷冻干燥酵母的基础上。我们不需要昂贵的设备和额外的试剂，通过改造酵母来生产红色番茄色素番茄红素，以应对霍乱病原体。我们设想，可以将工程酵母冷冻干燥，然后在全球范围内分发，以提供一种廉价、安全、简单和可靠的工具，用于在有感染风险的社区监测霍乱。如果成功，这个酵母平台将很容易重新部署，用于检测其他病原体。

 DESCRIPTION (provided by applicant): Diarrheal diseases are one of the top ten causes of death in developing countries, with V. cholerae being one of the principal bacterial causative agents annually infecting an estimated ~4 million and killing ~120,000 people. Although an easily treatable disease, cholera continues to cause fatal epidemics because in practice clinical detection rarely occurs outside remote hospitals and environmental detection in water supplies remains challenging. The state-of-the- art for cholera diagnostics are purified antibodies used as dipstick tests; unfortunately dipstick tests are prohibitively expensive and unstable for use directly in local communities where cholera is endemic. A new transformative mode of detection will be needed to generate an extremely cheap and widely distributable system for continuous local surveillance of cholera. We sought to overcome current obstacles to local diagnostics by using existing synthetic biology components to craft a new class of cheap and simple diagnostic built around freeze-dried yeast. We avoid the need for expensive equipment and additional reagents by engineering yeast to produce the red tomato pigment lycopene in response to the cholera pathogen. We envision that engineered baker's yeast can be freeze-dried and then globally distributed to provide an inexpensive, safe, simple and reliable tool for monitoring of cholera in communities at risk for infection. If successful, this yeast platform will be easily redeployable for the detection of other pathogens.