噬菌体sh-ab15519治疗耐碳青霉烯类鲍曼不动杆菌肺炎小鼠的实验.pdfVIP

噬菌体SH-Ab15519 治疗耐碳青霉烯类鲍曼不动杆 菌肺炎小鼠的实验研究 上海交通大学 杨宜锜，王睿，罗婷婷，王彦君 （上海交通大学医学院 免疫学与微生物学系，上海 200025 ；）1 何平 副教授 中文摘要：耐碳青霉烯类鲍曼不动杆菌（Carbapenem-resistant Acinetobacter baumannii，CRAB）是一类广谱抗药的 革兰阴性杆菌，主要感染免疫力低下的人群，其中以医院获得性肺炎最为普遍，病人死亡率高。噬菌体能特异性感染和裂解 细菌，具有替代抗生素治疗多耐药细菌感染的巨大潜力。实验基于临床收集来的48 株CRAB 宿主菌，从污水中提纯出鲍曼噬 菌体并对其形态学、宿主谱和全基因组进行分析，同时构建小鼠肺炎模型测定噬菌体的治疗效果。结果显示，提纯出的4 株 噬菌体宿主谱可同时覆盖现有87.5% (42/48)的耐药菌。基因测序结果显示噬菌体SH-Ab15519 是一种首次被发现的全新噬 菌体，基因序列中无耐药基因。动物实验显示，SH-Ab15519 通过滴鼻给药可以有效地救治致死性小鼠肺炎模型且无明显毒副 作用。结论表示噬菌体疗法能有效治疗耐药鲍曼不动杆菌引起的肺部感染，这为将来临床应用提供保障。 英文摘要：Carbapenems-resistant A. baumannii (CRAB) which is noted as a major pathogen associated with healthcare-associated infections has steadily developed beyond antibiotic control. To date, the result of nosocomial CRAB pneumonia control is still unsatisfied. The objective of this study was to investigate the efficacy and biosafety of using phages as a therapy against CRAB pneumonia in mice. An A.baumannii-specific lytic phage, SH-Ab15519, was isolated from the sewage based on 48 strains of CRAB collected within a tertiary care hospital, Shanghai, China. The genome of SH-Ab15519 was 40,439 bp (39.5% G+C) and it is a novel phage without containing the virulence or antibiotic resistance genes. The results of the mice curative experiment demonstrate that 9 intranasal administration of a single dose of SH-Ab15519 (10 PFU/mouse) after CRAB inoculation could rescue mice from fetal pneumonia. Compared to the control group, the phage-treated mice exhibited a lower level of CRAB burden in the lungs. In addition, these mice showed a decreasing proinflammation cytokines (TNF-, IL-6) level in the bronchoalveolar lavage fluid(BALF) and a healing lung lesion under microscopy. Our work demonstrates the potential