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用于裂解多种菌株的系统性噬菌体筛选。

Systematic bacteriophage selection for the lysis of multiple strains.

作者信息

Rieper Finja, Wittmann Johannes, Bunk Boyke, Spröer Cathrin, Häfner Melanie, Willy Christian, Müsken Mathias, Ziehr Holger, Korf Imke H E, Jahn Dieter

机构信息

Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Braunschweig, Germany.

Institute of Microbiology, Braunschweig University of Technology, Braunschweig, Germany.

出版信息

Front Cell Infect Microbiol. 2025 May 23;15:1597009. doi: 10.3389/fcimb.2025.1597009. eCollection 2025.

DOI:10.3389/fcimb.2025.1597009
PMID:40487314
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12141865/
Abstract

is an opportunistic pathogen causing severe infections of the lung, burn wounds and eyes. Due to its intrinsic high antibiotic resistance the bacterium is difficult to eradicate. A promising therapeutic option is the use of -specific bacteriophages. Thus, the implementation of a phage therapy requires their selection, production and systematic administration using multiple strains of the bacterial target. Here, we used 25 phages and tested their susceptibility on 141 different strains isolated from patients with different types of infection. Comparative host spectrum analyses were carried out using double agar overlay plaque assay (DPA) and planktonic killing assay (PKA), which resulted in 70% of the cases in the same host range. All phages were assigned to known phage genera, but some of the phages are new species. Isolated members of the genera , (myoviruses), , (myoviruses, jumbo phages), and (podoviruses) demonstrated great therapeutic potential due to strong lysis behavior on diverse strains. Seven phages were excluded for therapeutic purposes due to genetic determinants that confer lysogenicity. Due to automation with lower time expenditure in execution and analysis, PKA has the higher potential for implementation in diagnostics. Finally, different combinations of phages were tested with various strains. Highly efficient phage combinations eradicating multiple strains were found. Thus, a solid basis for the development of a broad host range phage therapy was laid.

摘要

是一种机会致病菌,可引起肺部、烧伤创面和眼部的严重感染。由于其固有的高抗生素抗性,这种细菌很难根除。一种有前景的治疗选择是使用特异性噬菌体。因此,实施噬菌体疗法需要对其进行选择、生产,并使用多种细菌靶标菌株进行系统给药。在这里,我们使用了25种噬菌体,并测试了它们对从不同类型感染患者中分离出的141种不同菌株的敏感性。使用双层琼脂覆盖噬菌斑测定法(DPA)和浮游菌杀灭测定法(PKA)进行了比较宿主谱分析,结果在70%的情况下宿主范围相同。所有噬菌体都被归类到已知的噬菌体属,但其中一些噬菌体是新物种。分离出的 属、 属(肌尾噬菌体)、 属、 属(肌尾噬菌体、巨型噬菌体)、 属和 属(短尾噬菌体)的成员,由于对多种菌株具有强烈的裂解行为,显示出巨大的治疗潜力。由于具有赋予溶原性的遗传决定因素,七种噬菌体被排除用于治疗目的。由于在执行和分析中时间消耗较低的自动化,PKA在诊断中具有更高的实施潜力。最后,测试了不同噬菌体组合对各种 菌株的效果。发现了能根除多种 菌株的高效噬菌体组合。因此,为开发广泛宿主范围的噬菌体疗法奠定了坚实基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/31c77e25aa34/fcimb-15-1597009-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/623388ddbdb6/fcimb-15-1597009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/30a8ba0c2529/fcimb-15-1597009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/f807f08275f1/fcimb-15-1597009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/95fa0b059486/fcimb-15-1597009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/82715a2f1759/fcimb-15-1597009-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/c80cfb3eb025/fcimb-15-1597009-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/31c77e25aa34/fcimb-15-1597009-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/623388ddbdb6/fcimb-15-1597009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/30a8ba0c2529/fcimb-15-1597009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/f807f08275f1/fcimb-15-1597009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/95fa0b059486/fcimb-15-1597009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/82715a2f1759/fcimb-15-1597009-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/c80cfb3eb025/fcimb-15-1597009-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/12141865/31c77e25aa34/fcimb-15-1597009-g007.jpg

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