基于表面诱导自组装的细菌感染检测与治疗策略研究

Intensive and frequent use of antibiotic drugs escalates bacterial resistance in both hospitals and communities. The rise of antibiotic resistance not only poses a great challenge for public health, but also compromises our ability to treat bacterial infectious disease. In this project, we plan to use the strategy of ‘surface-induced self-assembly’ to selective form peptidic hydrogel or nano-structures on the surface of bacterials, which results in bacteria cell death, while innocuous to human cells. We will synthesize the conjugates of peptide and antibiotics,which can selective form nanostructures on cell surface for the high affinity of bacteria surface and antibotics. The formed nanostructurs on cell surface could further self-assembly to form nanonet around bacteria, results in bacteria death. We will investigate the survival and proliferation rates at the surface of bacterials. We will use several techniques including TEM, confocal microscopy and SEM to characterize the formed hydrogel on bacteria surface. After demonstrated our concept in vitro, we will construct bacteria infected mice model to evaluate the activity of our designed conjugates of peptide and antibotics. This strategy will enhance the local concentration of aminoglycoside antibiotics and block bacterial transmission between material and information through bacteria surface modification. This project not only provides several candicates for killing bacteria, but also opens up a new way to solve the bacterial infection, especially drug resistance bacteria.

随着抗生素的滥用，细菌的抗药性逐步增强，细菌感染反复发作并导致各种并发症，严重威胁动物与人体健康。本项目拟采用“表面诱导自组装”的策略在细菌表面形成负载抗生素的多肽小分子水凝胶或纳米组装结构，达到有效清除感染部位细菌，而不影响正常细胞。本申请将能与细菌表面作用的氨基糖苷类抗生素通过与多肽凝胶因子化学反应形成“多肽凝胶因子-抗生素”轭合物，随后用于特异性地修饰细菌表面，使细菌表面带上成胶因子，再通过“表面诱导自组装”策略特异性的在细菌表面形成小分子水凝胶，并检测其对细菌生长与存活的影响。而后，采用透射电镜、激光共聚焦显微镜、扫描电镜等多种表征手段证实小分子水凝胶在细菌表面的形成，采用小鼠感染模型来评价轭合物表面组装在体内疗效。该策略通过细菌表面凝胶化，提高糖苷类抗生素局部浓度，阻隔细菌之间物质和信息传递，实现细菌感染的有效治疗，不仅开发了新的抗菌药物，还为解决细菌感染提供了新的思路。