Beta-内酰胺酶荧光探针及其在耐药菌检测中的应用

项目名称： Beta-内酰胺酶荧光探针及其在耐药菌检测中的应用

项目编号： No.21472048

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 谢贺新

作者单位： 华东理工大学

项目金额： 85万元

中文摘要： 近年来，由于抗生素的滥用，病菌的耐药情况正变得日益严重，受到越来越多人的关注。但现有的耐药菌检测方法通常耗时较长，难以实现快速检测。本课题以病菌产生的各种beta-内酰胺酶为靶标，开展有关于beta-内酰胺酶荧光探针的研究。为了实现对不同类型耐药菌的选择性检测，探针的设计从beta-内酰胺酶活性口袋的结构特点出发，再模拟现有beta-内酰胺类抗生素的取代基特征。通过系统而深入的探针结构与酶动力学关系研究来达到优化探针结构的目的，再结合新颖的多重荧光发射团释放体系来进一步增强荧光信号变化，发展同时具有高灵敏度和高选择性的beta-内酰胺酶荧光探针体系，应用在临床耐药病菌的快速检测中。本项目的成功实现，将有助于对耐药菌的监测和实现感染病人的个性化抗生素治疗，减少抗生素的滥用并最终大大减少耐药菌出现的几率。

中文关键词： beta-内酰胺酶；荧光探针；抗生素耐药；检测

英文摘要： Recently, antibiotic resistance, which is due in large part to the misuse or over-dose of antibiotics, has emerged as a major concern to the public. One of the major causes of antibiotic resistance is the generation of beta-lactamase in microbes, causing the degradation of beta-lactam-typed antibiotics. In this project, with the beta-lactamases in pathogenic bacteria as reporter, we focus on the development of beta-lactamase fluorogenic probes to selectively detect a range of antibiotic resistance. We design the probes by mimicking the characteristic structures of beta-lactam antibiotics to achieve high level of selectivities. And the probes would be further structurally optimized by systematically investigation of the relationship between the probe strutures and enzymatic kinetics. Additionally, the use of a multiple- fluorophore-releasing linker in the probes will be studied to further boost the sensitivities. Furter investigation of these probes with antibiotic-resistant microbes, even clinic samples will be performed to validate this novel detection system. The success of this project will deliver a handy approach for rapid dection of antibiotic resistance and even contribute to the point-of-care treatment of infected patients, reducing misuse or over-dose of antibiotic and thus minimizing the chance of antibiotic resistance.

英文关键词： beta-lactamase;fluorogenic probe;antibiotic resistance;detection