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