大肠杆菌易产生耐药性，本实验室前期研究发现岭南药材葫芦茶的酚类有效成分具有较强的抗菌性且无耐药性，但其作用机制和作用靶点尚未阐明。本课题以含CTX-M和fosA3大肠杆菌为模型，拟采用蛋白组学技术多角度研究葫芦茶提取物对耐药大肠杆菌的作用机理和药物作用靶点。通过差异蛋白组学方法探测药物对细菌生长、繁殖、代谢等环节蛋白质生成的影响,提出中药抗菌机理假设；再采用扫描电镜、RT-PCR、流式细胞仪、western blot等方法验证药物作用前后对细菌碱性磷酸酶（AKP）、电导率、胞外蛋白、蛋白合成有关酶和基因表达等因子变化分析中药对细菌细胞壁、细胞膜和蛋白质合成影响；通过傅里叶红外光谱仪、紫外光谱、圆二色谱和荧光光谱分析中药提取物对DNA、蛋白α螺旋、β-折叠、脂肪酸合成的影响，多角度阐明葫芦茶酚类对耐药菌作用机理，为探索中药的作用靶点和新药开发提供理论依据。

Escherichia coli were easy to produce antimicrobial resistance. We found that active phenolics of Gourd tea distributing Lingnan area had strong bacteriostatic effect and no drug resistance, but its mechanism and drug targets were not clear. In this paper, CTX-M and fosA3-Producing Escherichia coli as a model, proteomics technology would be used to research the action mechanism of Gourd tea extracts on drug-resistant Escherichia coli and targets of drug action from multiple perspectives. Effects of Gourd tea extracts on protein production during bacterial growth, reproduction and metabolism were studied by differential proteomics method, antibacterial mechanism hypothesis was put forward in in this paper. Then scanning electron microscopy (SEM),RT-PCR, flow cytometric method and western blot were used to observe the effects of Gourd tea extracts on bacterial cell wall, cell membrane and protein synthesis by analyzing changes of alkaline phosphatase (AKP), conductivity, extracellular protease, protein synthesis related enzymes and gene expression. By using Fourier transform infrared spectrometer(FTIR), ultraviolet spectroscopy, circular dichroism spectroscopy and fluorescence spectrum, the influence of Gourd tea extracts on DNA, alpha-helix , beta sheet and fatty acid synthesis were analyzed, the action mechanism of Gourd tea extracts on bacteria resistance from many aspects was clarified to provide a theoretical basis for exploring new drug targets and new drugs research.