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噬菌体 Henu3 的生物学特性及其抗性菌株的适应代价。

The Biological Characteristics of Phage Henu3 and the Fitness Cost Associated with Its Resistant Strains.

机构信息

Institute of Biomedical Informatics, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China.

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.

出版信息

Int J Mol Sci. 2024 Aug 27;25(17):9301. doi: 10.3390/ijms25179301.

Abstract

Tuberculosis (TB), caused by , is an infectious disease that seriously affects human life and health. Despite centuries of efforts to control it, in recent years, the emergence of multidrug-resistant bacterial pathogens of due to various factors has exacerbated the disease, posing a serious threat to global health. Therefore, a new method to control is urgently needed. Phages, viruses that specifically infect bacteria, have emerged as potential biocontrol agents for bacterial pathogens due to their host specificity. In this study, a phage, Henu3, was isolated from soil around a hospital. The particle morphology, biological characteristics, genomics and phylogeny of Henu3 were characterized. Additionally, to explore the balance between phage resistance and stress response, phage Henu3-resistant strains 0G10 and 2E1 were screened by sequence passage and bidirectional validation methods, which significantly improved the sensitivity of phage to antibiotics (cefotaxime and kanamycin). By whole-genome re-sequencing of strains 0G10 and 2E1, 12 genes involved in cell-wall synthesis, transporter-encoded genes, two-component regulatory proteins and transcriptional regulatory factor-encoded genes were found to have mutations. These results suggest that phage Henu3 has the potential to control pathogens, and phage Henu3 has the potential to be a new potential solution for the treatment of infection.

摘要

结核分枝杆菌(TB)是一种传染病,严重影响人类的生命和健康。尽管人们几个世纪以来一直努力控制它,但近年来,由于多种因素,结核分枝杆菌出现了耐药性细菌病原体,使这种疾病恶化,对全球健康构成严重威胁。因此,迫切需要一种新的方法来控制结核分枝杆菌。噬菌体是专门感染细菌的病毒,由于其宿主特异性,已成为细菌病原体的潜在生物控制剂。在这项研究中,从医院周围的土壤中分离出一种噬菌体 Henu3。对 Henu3 的粒子形态、生物学特性、基因组学和系统发育进行了表征。此外,为了探索噬菌体耐药性和应激反应之间的平衡,通过序列传递和双向验证方法筛选出噬菌体 Henu3 的抗性菌株 0G10 和 2E1,这显著提高了噬菌体对抗生素(头孢噻肟和卡那霉素)的敏感性。通过对菌株 0G10 和 2E1 的全基因组重新测序,发现参与细胞壁合成的 12 个基因、转运蛋白编码基因、双组分调节蛋白和转录调节因子编码基因发生了突变。这些结果表明,噬菌体 Henu3 有可能控制结核分枝杆菌病原体,并且噬菌体 Henu3 有可能成为治疗结核分枝杆菌感染的新的潜在解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3da4/11394830/3162ceb7109c/ijms-25-09301-g001.jpg

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