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从污水中分离的新型噬菌体的特性及其对碳青霉烯类耐药菌的疗效。

Characterization and efficacy against carbapenem-resistant of a novel phage from sewage.

机构信息

Weifang Key Laboratory of Respiratory Tract Pathogens and Drug Therapy, School of Life Science and Technology, Shandong Second Medical University, Weifang, China.

School of Pharmacy, Shandong Second Medical University, Weifang, China.

出版信息

Front Cell Infect Microbiol. 2024 Apr 22;14:1382145. doi: 10.3389/fcimb.2024.1382145. eCollection 2024.

Abstract

Carbapenem-resistant (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus , subfamily , and family . The results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.

摘要

近年来,耐碳青霉烯肠杆菌(CRAB)由于其对抗生素的耐药性迅速增加,已成为新的威胁,需要新的有效治疗方法来对抗这种病原体。噬菌体治疗被认为是治疗 CRAB 感染最有前途的替代方法。在这项研究中,从医院污水中分离并鉴定了一种新型噬菌体 Ab_WF01,它可以裂解临床 CRAB。还研究了噬菌体的感染复数、形态、一步生长曲线、稳定性、敏感性和裂解活性。噬菌体 Ab_WF01 的基因组大小为 41,317 bp,GC 含量为 39.12%,编码 51 个开放阅读框(ORFs)。噬菌体基因组中未检测到 tRNA、毒力和抗生素耐药基因。比较基因组和系统发育分析表明,噬菌体 Ab_WF01 是一个新的属、亚科和科的新种。结果表明,噬菌体 Ab_WF01 显著提高了 CRAB 感染(48 小时时从 0%增加到 70%)和小鼠(7 天内从 0%增加到 60%)的存活率。此外,感染后第 3 天,噬菌体 Ab_WF01 降低了炎症反应,在感染组织器官(肺、肝和脾)中,组织学损伤和细菌清除得到了明显改善。总之,这些结果表明,噬菌体 Ab_WF01 作为一种具有良好稳定性的潜在替代药物,具有治疗 CRAB 感染的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b80/11086170/d4c33079d099/fcimb-14-1382145-g001.jpg

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