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分离和鉴定 vB_kpnM_17-11,一种有效对抗碳青霉烯类耐药菌的新型噬菌体。

Isolation and Characterization of vB_kpnM_17-11, a Novel Phage Efficient Against Carbapenem-Resistant .

机构信息

Department of Pathogen Biology, School of Basic Medicine, Public Center Experimental Technology of Pathogen Biology, Southwest Medical University, Luzhou, China.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.

出版信息

Front Cell Infect Microbiol. 2022 Jul 5;12:897531. doi: 10.3389/fcimb.2022.897531. eCollection 2022.

Abstract

Phages and phage-encoded proteins exhibit promising prospects in the treatment of Carbapenem-Resistant (CRKP) infections. In this study, a novel phage vB_kpnM_17-11 was isolated and identified by using a CRKP host. vB_kpnM_17-11 has an icosahedral head and a retractable tail. The latent and exponential phases were 30 and 60 minutes, respectively; the burst size was 31.7 PFU/cell and the optimal MOI was 0.001. vB_kpnM_17-11 remained stable in a wide range of pH (4-8) and temperature (4-40°C). The genome of vB_kpnM_17-11 is 165,894 bp, double-stranded DNA (dsDNA), containing 275 Open Reading Frames (ORFs). It belongs to the family of , order Caudovirales, and has a close evolutionary relationship with phage PKO111. Sequence analysis showed that the 4530 bp of vB_kpnM_17-11 encodes a putative depolymerase. testing demonstrated that vB_kpnM_17-11 can decrease the number of by 10-fold. In a mouse model of infection, phage administration improved survival and reduced the number of in the abdominal cavity by 10-fold. In conclusion, vB_kpnM_17-11 showed excellent and performance against infection and constitutes a promising candidate for the development of phage therapy against CRKP.

摘要

噬菌体及其编码蛋白在治疗碳青霉烯类耐药 (CRKP) 感染方面具有广阔的应用前景。本研究采用 CRKP 宿主菌分离鉴定了一株新的噬菌体 vB_kpnM_17-11,其头部呈二十面体,尾部可收缩。潜伏期和对数生长期分别为 30 和 60 分钟,爆发量为 31.7PFU/细胞,最佳感染复数(MOI)为 0.001。vB_kpnM_17-11 在 pH 值(4-8)和温度(4-40°C)范围较宽的条件下保持稳定。vB_kpnM_17-11 的基因组为 165894bp,双链 DNA(dsDNA),包含 275 个开放阅读框(ORFs)。它属于长尾噬菌体科,噬菌目,与噬菌体 PKO111 具有密切的进化关系。序列分析表明,vB_kpnM_17-11 的 4530bp 编码一个假定的解聚酶。实验表明,vB_kpnM_17-11 能使细菌数量减少 10 倍。在感染小鼠模型中,噬菌体给药可提高存活率,并使腹腔内细菌数量减少 10 倍。综上所述,vB_kpnM_17-11 对 CRKP 感染具有良好的杀菌效果和治疗效果,是开发噬菌体治疗 CRKP 的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bf/9294173/64ee6ba7e918/fcimb-12-897531-g001.jpg

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