秀丽隐杆线虫-产碳青霉烯酶阴沟肠杆菌感染模型的建立及应用

Establishment and application of Caenorhabditis elegans-producing carbapenemase Enterobacter cloacae infection model

目的建立秀丽隐杆线虫-产碳青霉烯酶阴沟肠杆菌感染模型,并利用该模型筛选体内有效治疗阴沟肠杆菌感染的药物。方法将产碳青霉烯酶的阴沟肠杆菌与线虫共培养,建立线虫-产碳青霉烯酶阴沟肠杆菌感染模型,选用7种临床常见的抗菌药物(米诺环素、多西环素、庆大霉素、氨曲南、亚胺培南、替加环素和多黏菌素B)对感染后的线虫进行治疗,观察并记录线虫的生存状态,根据线虫的存活率评价不同药物的疗效。结果产碳青霉烯酶的阴沟肠杆菌能够感染线虫并致其死亡,通过荧光探针标记可见细菌在线虫肠道内定植生长。使用多黏菌素B、替加环素、米诺环素、多西环素治疗后,线虫的生存率与对照组相比显著提高。结论成功建立了秀丽隐杆线虫-产碳青霉烯酶阴沟肠杆菌感染模型,并将该模型用于体内抗菌药物活性的筛选。

Objective To establish a model of Enterobacter cloacae and carbapenem-producing Enterobacter cloacae infection and to use this model to screen effective drugs for the treatment of Enterobacter cloacae infections. Methods Carbapenemase-producing Enterobacter cloacae was used to co-culture with nematode to establish an infection model of Caenorhabditis elegans-carbapenemase-producing Enterobacter cloacae. Seven common antibacterial drugs （minocycline, gentamicin, aztreonam, imipenem, tigecycline, and polymyxin B） were used to treat the infected nematodes. The survival status of nematodes was observed and recorded. The efficacy of different drugs based on the survival rate of nematodes was evaluated. Results High concentrations of carbapenem-producing Enterobacter cloacae can infect nematodes and cause their death. Fluorescent probes showed that bacteria could grow colonies in the gut. The nematode survival rate in the treatment group with the use of polymyxin B, tigecycline, minocycline, and doxycycline was significantly improved compared with the control group. Conclusion The infection model of Caenorhabditis elegan-carbapenemase-producing Enterobacter cloacae was established, and can be used for in vivo screening of antimicrobial activity.