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新型K1荚膜依赖性噬菌体JSSK01及其解聚酶在多重耐药感染中的治疗和诊断潜力

Therapeutic and Diagnostic Potential of a Novel K1 Capsule Dependent Phage, JSSK01, and Its Depolymerase in Multidrug-Resistant Infections.

作者信息

Gattuboyena Naveen, Tsai Yu-Chuan, Lin Ling-Chun

机构信息

Master Program in Biomedical Sciences, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Road, Hualien 97004, Taiwan.

Institute of Medical Sciences, Tzu Chi University, No. 701, Sec. 3, Zhongyang Road, Hualien 97004, Taiwan.

出版信息

Int J Mol Sci. 2024 Nov 21;25(23):12497. doi: 10.3390/ijms252312497.

DOI:10.3390/ijms252312497
PMID:39684210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11641727/
Abstract

Bacteriophages are viruses that have the potential to combat bacterial infections caused by antimicrobial-resistant bacterial strains. In this study, we investigated a novel lytic bacteriophage, vB_EcoS_JSSK01, isolated from sewage in Hualien, Taiwan, which effectively combats multidrug-resistant (MDR) of the K1 capsular type. K1 is a major cause of severe extraintestinal infections, such as neonatal meningitis and urinary tract infections. Phage JSSK01 was found to have a genome size of 44,509 base pairs, producing approximately 123 particles per infected cell in 35 min, and was highly stable across a range of temperatures and pH. JSSK01 infected 59.3% of the MDR strains tested, and its depolymerase (ORF40) specifically degraded the K1 capsule in these bacteria. In a zebrafish model, JSSK01 treatment after infection significantly improved survival, with survival in the treated group reaching 100%, while that in the untreated group dropped to 10% after three days. The functional activity of depolymerase was validated using zone inhibition and agglutination tests. These results indicate that JSSK01 and its substrate-specific depolymerase have promising therapeutic and diagnostic applications against K1-encapsulated MDR infections.

摘要

噬菌体是一种有可能对抗由耐抗菌药物的细菌菌株引起的细菌感染的病毒。在本研究中,我们调查了一种从台湾花莲污水中分离出的新型裂解性噬菌体vB_EcoS_JSSK01,它能有效对抗K1荚膜型多重耐药菌(MDR)。K1是严重的肠外感染的主要原因,如新生儿脑膜炎和尿路感染。发现噬菌体JSSK01的基因组大小为44,509个碱基对,在35分钟内每个受感染细胞产生约123个粒子,并且在一系列温度和pH值范围内高度稳定。JSSK01感染了59.3%的测试MDR菌株,其解聚酶(ORF40)特异性降解这些细菌中的K1荚膜。在斑马鱼模型中,感染后用JSSK01治疗显著提高了存活率,治疗组的存活率达到100%,而未治疗组在三天后降至10%。使用抑菌圈和凝集试验验证了解聚酶的功能活性。这些结果表明,JSSK01及其底物特异性解聚酶在对抗K1包裹的MDR感染方面具有有前景的治疗和诊断应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/573f7fefbaf1/ijms-25-12497-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/7c33f6ea25c6/ijms-25-12497-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/878f1e39a9f3/ijms-25-12497-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/54ea2d61f7b7/ijms-25-12497-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/10cbecfda2f1/ijms-25-12497-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/573f7fefbaf1/ijms-25-12497-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/7c33f6ea25c6/ijms-25-12497-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/4c63e0b2d556/ijms-25-12497-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/878f1e39a9f3/ijms-25-12497-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9939/11641727/54ea2d61f7b7/ijms-25-12497-g004a.jpg
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本文引用的文献

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