表面诱导自组装凝胶化及其抗菌上的应用

Currently available antimicrobials have broad-spectrum killing ability to most of bacterial species, such indiscriminate killing of microbes can disrupt the ecological balance of indigenous microbial flora, likely are associated with various diseases including cancer. Thus, it is beneficial to develop new antimicrobial that solely kill pathogen without harming benign microorganisms. In this project, we plan to choose staphylococcus aureus as the target, and use the receptor on the bacterial surface as a trigger, not only facility the binding, also induced the self-assembly of peptide and subsequently hydrogelation. The resulting hydrogel could trap the bacterial and lead to bacterial inhibition. On the contrast, other benign microorganisms don’t have such specific receptor and fail to trigger hydrogelation, thus exhibit negligible inhibition. Multiply techniques including electron microscopy, fluorescence microscopy, and rheometer will be used to investigate that self-assembly and hydrogelation occur on the surface of bacterial, as well as the activity of bacterial after co-incubation with peptides. This proposal project will demonstrate that induces the peptides self-assemble selectively on pathogen’s surface and result in hydrogelation, lead to selectively inhibition of pathogen rather than other specifies. This project will provide a novel insight and approach for infection diseases.

目前可用的抗菌药物大多具有广谱抗菌性，这种不具有选择性的杀菌行为将严重破坏微生物菌群的生态平衡，甚至诱导包括癌症在内的各种疾病。因此开发靶向病原菌而不伤害益生菌的抗菌疗法具有很好的医学价值。本项目拟选择金黄色葡萄球菌为靶向对象，利用多肽分子与其表面受体的结合力，诱导多肽的自组装及水凝胶。形成的水凝胶可以包裹细菌从而抑制其活性。相反的是，其他有益菌由于不具有这种特定的受体，不能在相同浓度诱导多肽凝胶化，因而不受抑制。本项目将采用电镜、荧光显微镜、流变仪等多种技术手段验证多肽分子在细菌表面的组装和凝胶化，以及对其活性的影响。该项目通过病原菌表面诱导的自组装和凝胶化，实现选择性抑菌。这为细菌感染性疾病提供了一种新的思路和方法。

本研究计划拟采用“表面诱导自组装”策略特异性在金黄色葡萄球菌表面自组装形成多肽纳米纤维或者水凝胶，考察自组装多肽的成胶性能及理化性质；考察自组装多肽在金黄色葡萄球菌及其他细菌表面的自组装行为并评价其生物相容性。在2020-2022年间，项目负责人带领研究团队按照原定计划逐步合成并表征了自组装多肽的成胶性能及其理化性质；验证了自组装多肽对金黄色葡萄球菌具有靶向性，并可在其表面自组装形成纳米纤维；在细胞层面验证了自组装多肽具有良好的生物相容性并能够抑制细菌生物膜的形成。项目执行期间一共发表了标注该基金项目的SCI收录论文2篇，包括J. Nanobiotechnology. 1篇，Angew Chem Int Ed Engl 1篇；申请国家发明专利3项；培养了组组装多肽研究方面的2名优秀硕士生；项目负责人2020年入选“湖湘英才”和“芙蓉青年学者”，2022 年获“湖南省杰出青年基金”并入选国家万人计划“青年拔尖人才支持计划”。