功能核酸调控细菌生物膜的作用研究

As 65% human infections caused by bacteria are mainly related with biofilms, it is very important to control and remedy the biofilm clinically. Recently, a lot of progresses have been achieved that variously functional aptamers were used to treat the diseased infection, and also were efficient in adjusting and regulation of biofilm as our former works displayed. This project is to study the mechanism of interaction between aptamer and biofilm as follows: Firstly, the standard selective methods of aptamers will be established; Secondly, the interaction between aptamer and bacteria with flagellum/pilus will be analysed, and the formation and proliferation of biofilms will be also stated; Thirdly, the effects of aptamer in the produce and transmission of signal molecules of quorum sensing systems will be investigated, and the development and maturation of biofilm will be discussed as well; Finally,the main principles of aptamer-medicated anti-bacteria drugs/carbon nanometerials will be studied in the combating biofilm. The completion of the project should help to verify the molecular interaction between aptamer and biofilm, which will lay the foundation for further development of new nucleic acid drugs and provide an efficient way for biofilm treatment.

约65%的人类细菌感染与生物膜有关，因此控制和治疗生物膜在临床上具有十分重要的意义。近年来利用功能化核酸适配体治疗细菌感染取得了明显进展，我们的前期研究结果表明不同功能化适配体对控制细菌生物膜的形成，成熟和破坏具有较好的作用。本申请项目拟在前期实验的基础上进一步在以下四个方面开展核酸适配体调控生物膜作用的机制研究:（1）、核酸适配体筛选方法的建立与优化；（2）、分析适配体与具有鞭毛/菌毛细菌在粘附和扩散过程中的相互作用，探讨对生物膜形成和扩散中的作用机制。(3)、分析适配体在细菌群体感应中对信号分子产生和传递的影响，探讨对细菌生物膜发育成熟的作用机制。(4)、以核酸适配体作为药物运输载体，研究抗菌药物/碳纳米材料在控制细菌生物膜和治疗中的作用机制。该项目的实施将有助于从细胞和分子水平上阐述核酸适配体与生物膜相互作用机制，为进一步开发具有药物功能的核酸奠定基础。

人类约65%的细菌感染与细菌生物膜有关，因此控制和治疗生物膜在临床上具有十分重要的意义。四年来我们在利用功能化核酸适配体治疗细菌感染方面取得了明显进展，研究结果表明不同功能化适配体结合纳米粒子对控制细菌生物膜的形成，成熟和破坏具有较好的作用。通过筛选几种致病菌及生物标志分子的适配体并构建生物传感器，成功实现了对大肠杆菌、金黄色葡萄球菌、甲型副伤寒、氯霉素等的快速检测；同时, 经过分子生物学技术分析发现作为天然药物分子的小檗碱，可通过减少I型菌毛的数量影响细菌生物膜形成；将筛选的适配体与纳米粒子相结合，构建了一系列具有高特异性靶向纳米载药体系, 完成了抗细菌生物膜的研究；合成并构建了高黏附性、生物相容性和抗菌活性的高分子水凝胶—Fc-PAAM水凝胶，实现了抗细菌生物膜的作用, 为多模式抗细菌及生物膜研究提供了新的方法和技术。该课题执行以来共计发表SCI论文17篇，受到国内外同行高度关注，达到了预期目标。