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噬菌体溶菌酶作为对抗尿路致病性细菌的有前景且有效的候选物

Phage Endolysins as Promising and Effective Candidates for Use Against Uropathogenic .

作者信息

Wesołowski Wojciech, Łukasiak Aleksandra, Bloch Sylwia, Kuligowska Kaja, Neumann Julia, Lewandowska Natalia, Węglińska Emilia, Węgrzyn Grzegorz, Nejman-Faleńczyk Bożena

机构信息

Laboratory of Biology and Biotechnology of Bacteriophages, Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdansk, Poland.

BNF-New Bio Force Ltd., Kartuska 420a, 80-125 Gdańsk, Poland.

出版信息

Viruses. 2025 Apr 13;17(4):560. doi: 10.3390/v17040560.

DOI:10.3390/v17040560
PMID:40285003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12031403/
Abstract

The presented in silico and phylogenetic analysis of putative endolysins potentially produced by phages infecting uropathogenic (UPEC) demonstrates their remarkable diversity. These proteins exhibit significant variations in sequence length, molecular weight, isoelectric point, and stability, as well as diverse functional domains determining their enzymatic activity, including lysin, lysozyme, hydrolase, amidase, and peptidase functions. Due to their predicted lytic properties, endolysins hold great promise in combating UPEC bacteria, including those within biofilms, which are often highly resistant to conventional treatments. Despite their potential, several challenges hinder the full utilization of endolysins. These include the relatively small number of identified proteins, challenges in the annotation process, and the scarcity of studies evaluating their efficacy in vitro and in vivo against Gram-negative bacteria. In this work, we emphasize these challenges while also underlining the potential of endolysins as an effective tool against UPEC infections. Their effectiveness could be significantly enhanced when combined with agents that disrupt the outer membrane of these bacteria, making them a promising alternative or complement to existing antimicrobial strategies. Further research is necessary to fully explore their therapeutic potential.

摘要

对感染尿路致病性大肠杆菌(UPEC)的噬菌体可能产生的假定内溶素进行的计算机模拟和系统发育分析表明,它们具有显著的多样性。这些蛋白质在序列长度、分子量、等电点和稳定性方面表现出显著差异,以及决定其酶活性的不同功能域,包括溶素、溶菌酶、水解酶、酰胺酶和肽酶功能。由于其预测的裂解特性,内溶素在对抗UPEC细菌方面具有巨大潜力,包括生物膜中的细菌,这些细菌通常对传统治疗具有高度抗性。尽管内溶素有潜力,但仍有几个挑战阻碍了它们的充分利用。这些挑战包括已鉴定蛋白质数量相对较少、注释过程中的挑战,以及评估其体外和体内对革兰氏阴性菌功效的研究稀缺。在这项工作中,我们强调了这些挑战,同时也强调了内溶素作为对抗UPEC感染的有效工具的潜力。当与破坏这些细菌外膜的药物联合使用时,它们的有效性可能会显著提高,使其成为现有抗菌策略的有前途的替代方案或补充。有必要进行进一步研究以充分探索其治疗潜力。

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Microb Pathog. 2024 Dec;197:107058. doi: 10.1016/j.micpath.2024.107058. Epub 2024 Oct 23.
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The antibacterial activity of a novel highly thermostable endolysin, LysKP213, against Gram-negative pathogens is enhanced when combined with outer membrane permeabilizing agents.一种新型的高度耐热性溶菌酶LysKP213与外膜通透剂联合使用时,其对革兰氏阴性病原体的抗菌活性会增强。
Front Microbiol. 2024 Oct 8;15:1454618. doi: 10.3389/fmicb.2024.1454618. eCollection 2024.
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Antibacterial activity of bacteriophage-encoded endolysins against planktonic and biofilm cells of pathogenic Escherichia coli.噬菌体编码的溶菌素对致病性大肠杆菌浮游细胞和生物膜细胞的抗菌活性。
Microb Pathog. 2024 Aug;193:106780. doi: 10.1016/j.micpath.2024.106780. Epub 2024 Jul 3.
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Discovery and characterisation of new phage targeting uropathogenic Escherichia coli.新型靶向尿路致病性大肠杆菌噬菌体的发现与鉴定
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