【摘要】 本文旨在观察噬菌体对黏质沙雷菌感染小鼠的治疗作用,为噬菌体疗法应用于细菌性感染提供依据。以黏质沙雷菌为宿主菌,采用双层琼脂噬斑法从污水中分离和纯化裂解性噬菌体。将最小致死量的黏质沙雷菌经腹腔感染BALB/c小鼠后,立即腹腔注射不同剂量的噬菌体,观察动物的生存率并确定噬菌体的保护剂量。在动物感染后的不同时间(0、20、40、60和180min)观察噬菌体疗法对动物存活率的影响。将噬菌体和细菌同时或分别注射动物后,分析噬菌体在动物体内的药代动力学。结果显示,经噬斑法从污水中分离出1株裂解性噬菌体(命名为φSM9-3Y),电镜观察发现该噬菌体属有尾噬菌体目肌尾噬菌体科。动物腹腔感染黏质沙雷菌并立即给予噬菌体后发现,当噬菌体的保护剂量为108 PFU/ml时,动物的存活率为100%。动物感染后40和60min给予噬菌体(1010 PFU/ml)治疗,动物的存活率为60%。药代动力学表明,将噬菌体和细菌同时注入动物体内,在6h内噬菌体的滴度维持在1010 PFU/ml。结果提示,噬菌体对黏质沙雷菌所致动物腹腔内感染的治疗是有效的,提示针对细菌性感染的噬菌体疗法具有潜在的应用价值。更多还原

【Abstract】 This study aims to evaluate the efficacy of phage therapy against Serratia marcescens infections in mice and to provide the basis of phage therapy applied in bacterial infections.Double-agar overlay plaque method was employed to screen lytic phages from sewage,using Serratia marcescens isolates as hosts.Serratia marcescens strains at minimal lethal dose(MLD)were injected intraperitoneally(i.p.)into BALB/c mice and an i.p.of phage was followed.The survival rate of animals and protective dose of phage were examined at different time points(0,20,40,60 and 180 min)after the bacterial challenge.Pharmacokinetics of phages injected alone or with bacteria was analyzed respectively.The results showed that a lytic phage,designatedφSM9-3Y,was isolated and characterized from sewage.Electron microscope revealed that phageφSM9-3Y was in Siphoviridae family,Caudovirales order.After injection of Serratia marcescens isolates,immediate phage therapy at dose of 108 PFU/ml reached a protection rate of 100%.The protection rate was around 60% with a phage therapy(1010 PFU/ml)delivered 60 min after the infection.Pharmacokinetics analysis showed that phage titer in blood was maintained at level of 1010 PFU/ml within 6hwhen phages were injected i.p.together with bacteria.These data indicate that phages can save animals from pathogenic Serratia marcescens infection and suggest that phage therapy may be potentially used for the control of bacterial infections.更多还原