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研究重组噬菌体内溶素 AP50-31 和 LysB4 的抗菌特性,发现其对炭疽杆菌具有强大的杀菌作用。

Characterisation of the antibacterial properties of the recombinant phage endolysins AP50-31 and LysB4 as potent bactericidal agents against Bacillus anthracis.

机构信息

Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

The 5th R&D institute, Agency for Defense Development (ADD), Yuseong P.O.Box 35-5, Daejeon, 34186, Republic of Korea.

出版信息

Sci Rep. 2018 Jan 8;8(1):18. doi: 10.1038/s41598-017-18535-z.

Abstract

The recombinant phage endolysins AP50-31 and LysB4 were developed using genetic information from bacteriophages AP50 and B4 and were produced by microbial cultivation followed by chromatographic purification. Subsequently, appropriate formulations were developed that provided an acceptable stability of the recombinant endolysins. The bacteriolytic properties of the formulated endolysins AP50-31 and LysB4 against several bacterial strains belonging to the Bacillus genus including Bacillus anthracis (anthrax) strains were examined. AP50-31 and LysB4 displayed rapid bacteriolytic activity and broad bacteriolytic spectra within the Bacillus genus, including bacteriolytic activity against all the B. anthracis strains tested. When administered intranasally, LysB4 completely protected A/J mice from lethality after infection with the spores of B. anthracis Sterne. When examined at 3 days post-infection, bacterial counts in the major organs (lung, liver, kidney, and spleen) were significantly lower compared with those of the control group that was not treated with endolysin. In addition, histopathological examinations revealed a marked improvement of pathological features in the LysB4-treated group. The results of this study support the idea that phage endolysins are promising candidates for developing therapeutics against anthrax infection.

摘要

利用噬菌体 AP50 和 B4 的遗传信息开发了重组噬菌体内切酶 AP50-31 和 LysB4,并通过微生物培养和色谱纯化进行生产。随后,开发了合适的制剂,为重组内切酶提供了可接受的稳定性。研究了制剂内切酶 AP50-31 和 LysB4 对几种属于芽孢杆菌属的细菌菌株(包括炭疽芽孢杆菌(炭疽)菌株)的溶菌特性。AP50-31 和 LysB4 在芽孢杆菌属内具有快速的溶菌活性和广泛的溶菌谱,包括对所有测试的炭疽芽孢杆菌菌株的溶菌活性。当经鼻腔给药时,LysB4 完全保护 A/J 小鼠免受炭疽芽孢杆菌 Sterne 孢子感染的致死性。在感染后 3 天检查时,与未用内切酶治疗的对照组相比,主要器官(肺、肝、肾和脾)中的细菌计数明显降低。此外,组织病理学检查显示 LysB4 治疗组的病理特征明显改善。这项研究的结果支持这样一种观点,即噬菌体内切酶是开发炭疽感染治疗方法的有前途的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a60f/5758571/0f6a3073d163/41598_2017_18535_Fig1_HTML.jpg

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