Lactic Acid Bacteria that Detect & Inhibit Enterococci in the Mammalian GI Tract

描述（由申请人提供）：肠球菌是在人体肠道内自然生长的细菌。在过去的几十年里，这些病原体已经对我们最有效的抗生素产生了耐药性，包括万古霉素，这是一种治疗传染病的最后手段。耐万古霉素肠球菌（VRE）不会对健康个体造成疾病。但它确实会给住院病人带来严重的疾病，特别是那些接受抗生素治疗的病人。抗生素治疗消除了肠道中的许多“好”细菌 人类VRE抓住并填补这个真空，迅速从肠道扩散到血液，从那里到脾脏，肝脏，心脏。它们在那里生长并引起疾病，这些疾病不再容易用抗生素治疗。 我们通过基因工程制造乳酸 细菌（LAB）特异性靶向胃肠道（GI）内的肠球菌。我们建议将这些细胞机器人用于小鼠，并检查肠球菌是否从小鼠胃肠道中消失。我们追求三个具体目标：首先，我们设计出可以检测肠球菌的“智能”实验室。在检测时，工程化LAB产生并释放蛋白质。在第二个目标中，我们将这些蛋白质设计成对肠球菌是致命的。在第三个目标中，我们将检查我们的修饰LAB在小鼠中的功效。我们将用肠球菌感染小鼠，然后给予LAB。主要的假设是，工程LAB杀死肠球菌，并停止其在动物胃肠道内的定植。如果成功的话，这些实验可能会导致一个有前途的治疗策略，对肠球菌感染的发展。

DESCRIPTION (provided by applicant): Enterococci are bacteria that grow naturally inside human intestines. Over the last few decades, these pathogens have developed resistance to our most potent antibiotics, including vancomycin, an antibiotic of last resort for infectious disease. Vancomycin-resistant Enterococcus (VRE) does not cause illness to healthy individuals. But it does cause severe illness to hospital patients, especially the ones who have undergone antibiotic therapy. Antibiotic therapy eliminates a lot of the "good" bacteria in the gut of humans. VRE grab and fill this vacuum, spreading quickly from the intestines to the bloodstream and from there to the spleen, the liver, the heart. There they grow and cause disease that can no longer be easily treated with antibiotics. We genetically engineer lactic acid bacteria (LAB) to specifically target enterococcus inside gastrointestinal (GI) tracts. We propose to administer these cellbots to mice and examine if enterococcus vanishes from mouse GI tracts. We pursue three specific aims: First we engineer "smart" LAB that can detect enterococci. Upon detection, engineered LAB produce and release proteins. In the second aim, we engineer these proteins to be lethal to enterococci. In the third aim, we will examine the efficacy of our modified LAB in mice. We will infect mice with enterococcus and then administer LAB to them. The main hypothesis is that engineered LAB kill enterococci and stop their colonization inside animal GI tracts. If successful, these experiments can lead to the development of a promising therapeutic strategy against enterococcal infections.