【摘要】 噬茵体疗法在对抗多重耐药病原茵引起的感染方面具有很大的应用潜力。本研究从污水中分离到一株新的噬茵体,命名为NKP-1,并对噬茵体NKP-1的主要生物学特性进行研究。通过电镜观察确定NKP-1为短尾噬茵体,裂解试验表明该噬茵体为烈性噬茵体,具有很高的增值效率。体外试验表明它能够快速感染超强耐药的肺炎克雷伯菌株BAA-2146(NDM-1)并将其裂解。通过腹腔注射单一剂量的NKP-1(2×10~7 pfu/mL)就可以有效地保护BAA-2146(4×10~9 cfu/mL)感染引起的小鼠茵血症模型。在肺炎克雷伯菌BAA-2146与噬菌体NKP-1体外共同培养的过程中,我们分离到对该噬茵体具有抗性的突变菌株,通过动物试验确定该突变株表现为极低的毒力,且不影响NKP-1的治疗效果。本研究为利用噬菌体治疗多重耐药菌感染提供了理论基础与试验依据。更多还原

【Abstract】 Bacteriophage therapy could be an alternative to conventional antibiotic therapy against pathogens which are resistant to multiple antibiotics.In this study,a novel phage was isolated from sewage,termed NKP-1,which can replicate and lyse highly antibiotic resistant Klebsiella pneumoniae BAA-2146(harboring the NDM-1 carbapenemase). Basic characterization of NKP-1 demonstrated that the phage lysed BAA-2146 in vitro and in vivo.The phage resistance variant was found and isolated from BAA-2146 cultures when exposed to NKP-1,but the determination of MLD demonstrated an avirulent phage resistant variant.NKP-1 also displayed an ability in controlling BAA-2146 in a murine model of bacteremia.Bacteremic mice infected by lethal dose of BAA-2146(4×10~9 cfu/mL) were protected effectively by intraperitoneal administration of a single dose of NKP-1(2×10~7 pfu/mL).This novel phage have a great therapeutic potential as an antimicrobial agent target at antibiotic-resistant K.pneumoniae,and more importantly, this finding provides more forcible evidence towards the therapeutic use of phages to combat multi-drug resistant bacteria.更多还原