Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, Singapore.
J Mol Biol. 2020 May 1;432(10):3137-3148. doi: 10.1016/j.jmb.2020.03.029. Epub 2020 Apr 2.
Bacterial motility is related to many cellular activities, such as cell migration, aggregation, and biofilm formations. The ability to control motility and direct the bacteria to certain location could be used to guide the bacteria in applications such as seeking for and killing pathogen, forming various population-level patterns, and delivering of drugs and vaccines. Currently, bacteria motility is mainly controlled by chemotaxis (prescribed chemical stimuli), which needs physical contact with the chemical inducer. This lacks the flexibility for pattern formation as it has limited spatial control. To overcome the limitations, we developed blue light-regulated synthetic genetic circuit to control bacterial directional motility, by taking the advantage that light stimulus can be delivered to cells in different patterns with precise spatial control. The circuit developed enables programmed Escherichia coli cells to increase directional motility and move away from the blue light, i.e., that negative phototaxis is utilized. This further allows the control of the cells to form aggregation with different patterns. Further, we showed that the circuit can be used to separate two different strains. The demonstrated ability of blue light-controllable gene circuits to regulate a CheZ expression could give researchers more means to control bacterial motility and pattern formation.
细菌的运动性与许多细胞活动有关,例如细胞迁移、聚集和生物膜的形成。控制运动性并将细菌引导至特定位置的能力可用于指导细菌在以下应用中发挥作用,例如寻找和杀死病原体、形成各种群体水平的模式以及药物和疫苗的输送。目前,细菌的运动性主要通过化学趋性(规定的化学刺激)来控制,这需要与化学诱导剂进行物理接触。由于空间控制有限,这种方法缺乏形成图案的灵活性。为了克服这些限制,我们利用光刺激可以通过精确的空间控制以不同模式传递到细胞的优势,开发了蓝光调控的合成遗传回路来控制细菌的定向运动性。该回路使编程的大肠杆菌细胞增加了定向运动性并远离蓝光,即利用了负趋光性。这进一步允许控制细胞以不同的模式形成聚集。此外,我们表明该回路可用于分离两种不同的菌株。展示的蓝光可控基因回路调节 CheZ 表达的能力为研究人员提供了更多控制细菌运动性和模式形成的手段。