Development of a First-in-Class Antibiotic Targeting the Biosynthesis of the Outer Envelope of Gram-Negative Bacteria

细菌感染的有效治疗是现代医学的重要组成部分。为此，抗生素在拯救数百万人的生命方面发挥了核心作用。抗生素抗药性--当细菌发生变化，导致抗生素不再起作用时，抗生素的增长速度非常危险，并构成我们这个时代最大的公共卫生威胁之一。特别令人担忧的是革兰氏阴性细菌所表现出的耐药性水平。50多年来，没有一种针对革兰氏阴性菌的新抗生素被批准。我们正在使用系统生物学和机器学习来建立大肠杆菌--一种革兰氏阴性菌--的详细计算模型。我们使用该模型来识别传统抗菌药物发现方法遗漏的革兰氏阴性细菌中的易受攻击的点(“药物靶点”)。该项目基于开发一种针对使用我们的模型确定的一流靶点的药物。如果成功，该项目将代表着一种治疗革兰氏阴性感染的新型抗生素。

Effective treatment of bacterial infections is an essential component of modern medicine. To that end, antibiotics have played a central role in saving millions of lives. Antibiotic resistance - when bacteria change so that antibiotics no longer work, is growing at a dangerously high rate and poses one of the greatest public health threats of our time. Of particular concern are the resistance levels exhibited by the Gram-negative group of bacteria. No new class of antibiotic against Gram- negative bacteria has been approved for over 50 years.We are using systems biology and machine learning to build a detailed computational model of Escherichia coli - a type of Gram-negative bacteria. We use the model to identify vulnerable points ("drug targets") in Gram-negative bacteria that are missed by conventional antibacterial discovery approaches. The project is based on developing a drug against a first-in-class target identified using our model. If successful, the project would represent a new class of antibiotic to treat Gram-negative infections.