Li Haoran, Zhang Shanshan, Yin Jinyan, Wang Gege, Wang Qi, Xia Yongzhen, Li Lixiang, Qi Qingsheng, Wang Qian
National Glycoengineering Research Center, Shandong University, Qingdao, P. R. China.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao, P. R. China.
Gut Microbes. 2025 Dec;17(1):2530156. doi: 10.1080/19490976.2025.2530156. Epub 2025 Jul 6.
Rapid development of synthetic biology has led to engineered probiotics to address the growing concern of infectious diseases and cancer. Dual or multiple bacterial infections are becoming more frequent, but there are few treatment options because complex approaches are needed to address different disease mechanisms. In this study, we designed a minimal logic gate to program Nissle 1917 to detect and treat the disease caused by and . Two orthogonal gene circuits were verified to detect and kill the two pathogens, respectively. The "AND" gate was designed and engineered to achieve remarkable chemotaxis and killing effects in vitro when both pathogens existed. Then, we demonstrated the preventive and therapeutic effectiveness of the programmed EcN against and in a murine model of intestinal infection. The proof-of-concept of our programmed EcN strategy demonstrates an exciting potential method for preventing and treating dual-bacterial infection.
合成生物学的快速发展催生了工程益生菌，以应对人们对传染病和癌症日益增长的担忧。双重或多重细菌感染正变得越来越频繁，但由于需要复杂的方法来应对不同的疾病机制，治疗选择很少。在本研究中，我们设计了一个最小逻辑门，对Nissle 1917进行编程，以检测和治疗由[具体病原体1]和[具体病原体2]引起的疾病。验证了两个正交基因回路分别检测和杀死这两种病原体。设计并构建了“与”门，以在两种病原体同时存在时在体外实现显著的趋化和杀伤效果。然后，我们在小鼠肠道感染模型中证明了编程后的大肠杆菌Nissle 1917对[具体病原体1]和[具体病原体2]的预防和治疗效果。我们的编程大肠杆菌Nissle 1917策略的概念验证证明了一种用于预防和治疗双重细菌感染的令人兴奋的潜在方法。
