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

有效治疗细菌感染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。抗生素耐药性-当细菌发生变化，使抗生素不再起作用时，正在以危险的高速度增长，并构成我们这个时代最大的公共卫生威胁之一。特别令人关注的是革兰氏阴性菌群表现出的耐药性水平。在过去的50年里，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一个详细的大肠杆菌计算模型-一种革兰氏阴性菌。我们使用该模型来识别革兰氏阴性菌中的脆弱点（“药物靶点”），这些点被传统的抗菌药物发现方法所遗漏。该项目是基于开发一种针对使用我们的模型确定的一流目标的药物。如果成功，该项目将代表一类新的抗生素来治疗革兰氏阴性菌感染。

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.