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利用牛源微生物酶防治生物膜相关型肺炎克雷伯菌感染

Combating biofilm-associated Klebsiella pneumoniae infections using a bovine microbial enzyme.

机构信息

Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, Karnataka, India.

Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India.

出版信息

NPJ Biofilms Microbiomes. 2024 Nov 5;10(1):119. doi: 10.1038/s41522-024-00593-7.

DOI:10.1038/s41522-024-00593-7
PMID:39500915
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11538315/
Abstract

The emergence of multidrug-resistant Klebsiella pneumoniae poses significant clinical challenges with limited treatment options. Biofilm is an important virulence factor of K. pneumoniae, serving as a protective barrier against antibiotics and the immune system. Here, we present the remarkable ability of a bovine microbial enzyme to prevent biofilm formation (IC 2.50 μM) and degrade pre-formed K. pneumoniae biofilms (EC 1.94 μM) by degrading the matrix polysaccharides. The treatment was effective against four different clinical K. pneumoniae isolates tested. Moreover, the enzyme significantly improved the biofilm sensitivity of a poorly performing broad-spectrum antibiotic, meropenem, and immune cells, resulting in facile biofilm clearance from the mouse wound infection. Notably, well-known powerful enzymes of the same class, cellulase, and α-amylase, were nearly inactive against the K. pneumoniae biofilms. The enzyme exhibited antibiofilm activity without showing toxicity to the mammalian and microbial cells, highlighting the potential of the enzyme for in vivo applications.

摘要

耐多药肺炎克雷伯菌的出现带来了重大的临床挑战,治疗选择有限。生物膜是肺炎克雷伯菌的一个重要毒力因子,它作为一种对抗抗生素和免疫系统的保护屏障。在这里,我们展示了一种牛源微生物酶的显著能力,该酶可以通过降解基质多糖来预防生物膜的形成(IC 2.50 μM)和降解已形成的肺炎克雷伯菌生物膜(EC 1.94 μM)。该治疗方法对四种不同的临床分离肺炎克雷伯菌有效。此外,该酶还显著提高了广谱抗生素美罗培南和免疫细胞对生物膜的敏感性,从而易于从小鼠伤口感染中清除生物膜。值得注意的是,同类型的两种知名强力酶,纤维素酶和α-淀粉酶,对肺炎克雷伯菌生物膜几乎没有活性。该酶表现出抗生物膜活性而对哺乳动物和微生物细胞没有显示出毒性,突出了该酶在体内应用的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/3f8108c3adea/41522_2024_593_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/12e5acd7dc06/41522_2024_593_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/43f05a8c74aa/41522_2024_593_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/86e146747c22/41522_2024_593_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/45ecdf544b96/41522_2024_593_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/2168910b0740/41522_2024_593_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/1b04c05209af/41522_2024_593_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/3f8108c3adea/41522_2024_593_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/12e5acd7dc06/41522_2024_593_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/43f05a8c74aa/41522_2024_593_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/86e146747c22/41522_2024_593_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/45ecdf544b96/41522_2024_593_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/2168910b0740/41522_2024_593_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/1b04c05209af/41522_2024_593_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb7/11538315/3f8108c3adea/41522_2024_593_Fig7_HTML.jpg

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