目的建立秀丽隐杆线虫一甲氧西林耐药金黄色葡萄球菌感染模型,筛选抗耐药菌感染的活性化合物。方法利用耐药菌对线虫进行感染,建立液体条件感染和抗生素救治模型,通过观察感染线虫的存活情况,考察筛选样品活性。结果对456个样品进行考察,发现化合物sipi8294在浓度为16gg/mL时,可以使感染线虫存活率达到60%左右。通过联合用药实验发现,8μg/mL sipi8294和8gg/mL氨苄西林联用,可以使线虫存活率提高N80%以上(vs.8μg/mL氨苄西林组,P〈0.01)。sipi8294与青霉素类药物联用,具有明显的增效作用。结论该模型能反映病原菌在线虫体内的耐药性,并可以用于化合物的筛选,发现具有抗感染或是辅助抗感染作用的化合物。
Objective To establish a C. elegans-MRSA infective model, and screen anti-infective compounds. Methods Worms infected with drug resistant bacteria were treated by antibiotics. We investigated the activity of the screening compounds using this model to measure survival rate. Results We used above method to screen 456 compounds and found that sipi8294 at 16~tg/mL elevated the survival rate of infected nematodes to 60%. In combination experiment, we found sipi8294 combination with 13-1actams antibiotics could significantly increase the effect of anti-infection, for example, sipi8294 at 8~tg/mL combination with 8μg/mL ampicillin could increase survival rate more than 80% (vs. 8μg/mL ampicillin, P〈0.01). Conclusion The model reflects the drug resistance of methicillin-resistant Staphylococcus aureus in C elegans and could be used to screen antibacterial compounds and synergy anti-infective compounds.