Activity of GS-linked chimeric endolysin CHAPk-SH3bk against methicillin-resistant Staphylococcus aureus biofilms: an in-vitro, ex-vivo and in-vivo study.

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

npj Biofilms and Microbiomes Pub Date : 2025-06-03 DOI:10.1038/s41522-025-00728-4

Manisha Behera, Priyanka Singh, Anita Kamra Verma, Sachinandan De, Soma M Ghorai

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引用次数: 0

Abstract

The evolution of antibiotic resistance and the propensity of methicillin-resistant Staphylococcus aureus to form biofilms impedes antibiotic therapy, which enkindles the rummage for novel therapeutic agents like bacteriophage endolysins. This study investigates the biofilm degradation activity of novel chimeric endolysin CHAPk-SH3bk compared to single domain construct CHAPk. The in-vitro biofilm degradation assay displayed higher antibiofilm activity of CHAPk-SH3bk compared to CHAPk on glass and steel surfaces. Treatment of CHAPk-SH3bk effectively inhibited biofilm formation of hospital-associated and bovine-origin MRSA. The in-vivo results displayed a higher reduction of 24 h MRSA-biofilm using CHAPk-SH3bk compared to CHAPk in mice skin infection model. Further, confocal laser scanning microscopy, scanning electron microscopy, and immunohistochemistry confirmed the in-vivo results. The study indicated that attachment of SH3b using glycine-serine linker to CHAPk increased the catalytic domains biofilm reduction ability. The study demonstrates that construction of novel chimeric endolysins by shuffling parental endolysin domains may increase their antibiofilm activity.

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gs连接嵌合内溶素CHAPk-SH3bk对耐甲氧西林金黄色葡萄球菌生物膜的活性：体外、离体和体内研究

抗生素耐药性的进化和耐甲氧西林金黄色葡萄球菌形成生物膜的倾向阻碍了抗生素治疗，这引发了对噬菌体内毒素等新型治疗药物的寻找。本文研究了新型嵌合内溶素CHAPk- sh3bk的生物膜降解活性，并与单结构域结构体CHAPk进行了比较。体外生物膜降解实验表明，CHAPk- sh3bk在玻璃和钢表面的抗膜活性高于CHAPk。CHAPk-SH3bk治疗可有效抑制医院相关和牛源MRSA的生物膜形成。体内实验结果显示，与小鼠皮肤感染模型中的CHAPk相比，CHAPk- sh3bk对24小时mrsa生物膜的减少率更高。此外，共聚焦激光扫描显微镜、扫描电镜和免疫组织化学证实了体内结果。研究表明，甘氨酸-丝氨酸连接体将SH3b附着在CHAPk上增加了催化结构域生物膜还原能力。研究表明，通过重组亲本内溶素结构域构建新型嵌合内溶素可提高其抗膜活性。

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来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.