Zhou Yu-meng, Shao Lei, Li Ji-an, Han Li-zhong, Cai Wai-jiao, Zhu Chun-bao, Chen Dai-jie
State Key Lab for New Drug and Pharmaceutical Processes, Shanghai Institute of Pharmaceutical Industry.
Biosci Biotechnol Biochem. 2011;75(9):1746-51. doi: 10.1271/bbb.110290. Epub 2011 Sep 7.
As a large number of multidrug-resistant bacteria have emerged, and there is an urgent need for the development of new antibacterial agents. In this study, we developed a liquid-based slow killing assay to be carried out in standard 96-well microtiter plates. This screening method was designed to facilitate high-throughput screening of small molecules and extracts. In antibiotic rescue assays, the Caenorhabditis elegans multidrug-resistant Pseudomonas aeruginosa infection model displayed a high degree of drug resistance in vivo and in vitro. We used the method to screen 1,300 extracts, and found 36 extracts (2.7%) which prolonged the survival of infected nematodes, and four (0.3%) of these extracts showed in vitro and in vivo anti-multidrug resistant P. aeruginosa activity. These results indicate that the whole-animal C. elegans multidrug-resistant bacterial model can be used to screen antibacterial compounds, and can also be useful for bioactive compounds which most likely cannot be identified in vitro.
由于大量耐多药细菌的出现,迫切需要开发新的抗菌剂。在本研究中,我们开发了一种基于液体的缓慢杀伤试验,可在标准的96孔微量滴定板中进行。这种筛选方法旨在促进小分子和提取物的高通量筛选。在抗生素挽救试验中,秀丽隐杆线虫耐多药铜绿假单胞菌感染模型在体内和体外均表现出高度耐药性。我们使用该方法筛选了1300种提取物,发现36种提取物(2.7%)延长了受感染线虫的存活时间,其中4种(0.3%)提取物在体外和体内均表现出抗耐多药铜绿假单胞菌活性。这些结果表明,全动物秀丽隐杆线虫耐多药细菌模型可用于筛选抗菌化合物,也可用于体外最有可能无法鉴定的生物活性化合物。