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噬菌体和噬菌体编码的解聚酶在小鼠脓毒症和烧伤皮肤感染模型中对K9型细菌表现出抗菌活性。

Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type in Mouse Sepsis and Burn Skin Infection Models.

作者信息

Borzilov Alexander I, Volozhantsev Nikolay V, Korobova Olga V, Kolupaeva Lyubov V, Pereskokova Evgenia S, Kombarova Tatiana I, Shneider Mikhail M, Miroshnikov Konstantin A, Dyatlov Ivan A, Popova Anastasia V

机构信息

State Research Center for Applied Microbiology and Biotechnology, City District Serpukhov, Moscow Region, 142279 Obolensk, Russia.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.

出版信息

Viruses. 2025 Jan 6;17(1):70. doi: 10.3390/v17010070.

DOI:10.3390/v17010070
PMID:39861859
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11768871/
Abstract

is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn skin infection models. In the mouse sepsis model, in the case of prevention or early treatment, a single K9-specific phage or recombinant depolymerase injection was able to protect 100% of the mice after parenteral infection with a lethal dose of of the K9-type, with complete eradication of the pathogen. In the case of delayed treatment, mouse survival decreased to 70% when injected with the phage and to 40% when treated with the recombinant enzyme. In the mouse burn skin infection model, the number of cells on the surface of the wound and in the deep layers of the skin decreased by several-fold after treatment with both the K9-specific phage and the recombinant depolymerase. The phage and recombinant depolymerase were highly stable and retained activity under a wide range of temperatures and pH values. The results obtained contribute to expanding our understanding of the in vivo therapeutic potential of specific phages and phage-derived depolymerases interacting with of different capsular types.

摘要

是一种广泛分布的医院病原体,可引起各种急慢性感染,尤其是在免疫功能低下的患者中。在本研究中,使用体内小鼠败血症和烧伤皮肤感染模型评估了K9特异性烈性噬菌体AM24和噬菌体编码的解聚酶DepAPK09的活性。在小鼠败血症模型中,在预防或早期治疗的情况下,单次注射K9特异性噬菌体或重组解聚酶能够在经肠外感染致死剂量的K9型后保护100%的小鼠,病原体被完全根除。在延迟治疗的情况下,注射噬菌体时小鼠存活率降至70%,用重组酶治疗时降至40%。在小鼠烧伤皮肤感染模型中,用K9特异性噬菌体和重组解聚酶治疗后,伤口表面和皮肤深层的细胞数量减少了几倍。噬菌体和重组解聚酶高度稳定,在广泛的温度和pH值范围内保持活性。获得的结果有助于扩大我们对特定噬菌体和噬菌体衍生的解聚酶与不同荚膜类型的相互作用的体内治疗潜力的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/c2305cb6056b/viruses-17-00070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/0f2c6c836131/viruses-17-00070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/c4ec4ee0cbb1/viruses-17-00070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/c2305cb6056b/viruses-17-00070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/0f2c6c836131/viruses-17-00070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/c4ec4ee0cbb1/viruses-17-00070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59eb/11768871/c2305cb6056b/viruses-17-00070-g003.jpg

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