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噬菌体工程靶向治疗多重耐药

Phage Engineering for Targeted Multidrug-Resistant .

机构信息

Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250000, China.

出版信息

Int J Mol Sci. 2023 Jan 27;24(3):2459. doi: 10.3390/ijms24032459.

DOI:10.3390/ijms24032459
PMID:36768781
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10004113/
Abstract

The lytic bacteriophages have potential application value in the treatment of bacterial infections. However, the narrow host spectrum of these phages limits their range of clinical application. Here, we demonstrate the use of scarless Cas9-assisted recombination (no-SCAR) gene-editing technology to regulate phage-host range. We used phage PHB20 as the scaffold to create agents targeting different multidrug-resistant by replacing its phage tail fiber gene (ORF40). The engineered phages were polyvalent and capable of infecting both the original host bacteria and new targets. Phage-tail fiber genes can be amplified by PCR to construct a recombinant phage PHB20 library that can deal with multidrug-resistant bacteria in the future. Our results provide a better understanding of phage-host interactions, and we describe new anti-bacterial editing methods.

摘要

溶菌噬菌体在治疗细菌感染方面具有潜在的应用价值。然而,这些噬菌体的宿主谱狭窄限制了它们的临床应用范围。在这里,我们展示了无痕 Cas9 辅助重组(no-SCAR)基因编辑技术在调节噬菌体宿主范围方面的应用。我们使用噬菌体 PHB20 作为支架,通过替换其噬菌体尾纤维基因(ORF40)来创建针对不同多药耐药菌的靶向药物。工程噬菌体具有多价性,能够感染原始宿主细菌和新的靶标。噬菌体尾纤维基因可以通过 PCR 扩增来构建重组噬菌体 PHB20 文库,以应对未来的多药耐药菌。我们的研究结果加深了对噬菌体-宿主相互作用的理解,并描述了新的抗菌编辑方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/8ebdb74672e4/ijms-24-02459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/574a8143e1b6/ijms-24-02459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/b8bbe007d8fc/ijms-24-02459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/8ebdb74672e4/ijms-24-02459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/574a8143e1b6/ijms-24-02459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/b8bbe007d8fc/ijms-24-02459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ba/10004113/8ebdb74672e4/ijms-24-02459-g003.jpg

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