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抗菌肽AMP-17可诱导对系统性念珠菌病的保护作用,并与氟康唑协同作用对抗生物膜。

Antimicrobial peptide AMP-17 induces protection against systemic candidiasis and interacts synergistically with fluconazole against biofilm.

作者信息

Sun Chaoqin, Zhu Lijuan, Yang Longbing, Tian Zhuqing, Jiao Zhenlong, Huang Mingjiao, Peng Jian, Guo Guo

机构信息

School of Basic Medical Sciences, Key Laboratory of Microbio and Infectious Disease Prevention & Control, Guizhou Medical University, Guiyang, China.

Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China.

出版信息

Front Microbiol. 2024 Nov 1;15:1480808. doi: 10.3389/fmicb.2024.1480808. eCollection 2024.

DOI:10.3389/fmicb.2024.1480808
PMID:39552641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11564183/
Abstract

, a common commensal and opportunistic fungal pathogen in humans, can occasionally progress to disseminated candidiasis which is a serious condition with a high morbidity and fatality rate. The emergence of drug-resistant fungal strains compels us to look for an efficient treatment solution. Our earlier studies have demonstrated that the unique antimicrobial peptide AMP-17 from has a strong antifungal impact on . Here, we verified the therapeutic effects of AMP-17 on systemic candidiasis and the peptide interacts with fluconazole, a common antifungal medication, to treat systemic candidiasis. In the disseminated candidiasis model of and mice challenged with , AMP-17 increased the survival rates of infected larvae and mice to 66.7 and 75%, respectively. Furthermore, the peptide lowered the load of in the infected larvae and the kidneys of the mice by nearly 90%. Additional histological examination and measurements of plasma cytokines showed that the injection of AMP-17 markedly reduced the inflammatory response and balanced cytokine expression. Furthermore, checkerboard micro dilution experiments demonstrated that AMP-17 and fluconazole worked in synergy to inhibit in the biofilm mode. According to morphological studies, AMP-17 and fluconazole together decreased the production of hyphae throughout the biofilm formation process, loosening the mature biofilms' structure and lowering the amount of carbohydrates in the extracellular matrix (ECM) of the biofilms. Taken together, these results showed that AMP-17 would be a viable treatment for systemic candidiasis and might be a different approach to combating biofilm, either by itself or in conjunction with fluconazole.

摘要

白色念珠菌是人类常见的共生及机会性真菌病原体,偶尔会发展为播散性念珠菌病,这是一种严重疾病,发病率和死亡率很高。耐药真菌菌株的出现迫使我们寻找一种有效的治疗方案。我们早期的研究表明,来自[具体来源]的独特抗菌肽AMP - 17对白色念珠菌有很强的抗真菌作用。在此,我们验证了AMP - 17对系统性念珠菌病的治疗效果,并且该肽与常见抗真菌药物氟康唑相互作用来治疗系统性念珠菌病。在白色念珠菌和受其攻击的小鼠的播散性念珠菌病模型中,AMP - 17将感染幼虫和小鼠的存活率分别提高到了66.7%和75%。此外,该肽使感染幼虫和小鼠肾脏中的白色念珠菌载量降低了近90%。额外的组织学检查和血浆细胞因子测量表明,注射AMP - 17显著降低了炎症反应并平衡了细胞因子表达。此外,棋盘微量稀释实验表明,AMP - 17和氟康唑协同作用以生物膜模式抑制白色念珠菌。根据形态学研究,AMP - 17和氟康唑共同降低了白色念珠菌整个生物膜形成过程中菌丝的产生,使成熟生物膜的结构松弛,并降低了生物膜细胞外基质(ECM)中碳水化合物的含量。综上所述,这些结果表明AMP - 17可能是治疗系统性念珠菌病的一种可行方法,并且可能是对抗白色念珠菌生物膜的一种不同途径,无论是单独使用还是与氟康唑联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/2348933c55fa/fmicb-15-1480808-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/b4448eedd819/fmicb-15-1480808-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/169918c96d11/fmicb-15-1480808-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/8de31896f710/fmicb-15-1480808-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/13e7f65062fe/fmicb-15-1480808-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/46eb86dcd5c4/fmicb-15-1480808-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/2348933c55fa/fmicb-15-1480808-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/b4448eedd819/fmicb-15-1480808-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/169918c96d11/fmicb-15-1480808-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/8de31896f710/fmicb-15-1480808-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/13e7f65062fe/fmicb-15-1480808-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/46eb86dcd5c4/fmicb-15-1480808-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7a/11564183/2348933c55fa/fmicb-15-1480808-g006.jpg

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本文引用的文献

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[Identification of the target site of antimicrobial peptide AMP-17 against ].[抗菌肽AMP-17作用靶点的鉴定] (原文句子不完整,括号内为补充完整后的意译)
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The Antimicrobial Peptide AMP-17 Derived from Inhibits Biofilm Formation and Eradicates Mature Biofilm in .
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The prophylactic effects of monoclonal antibodies targeting the cell wall Pmt4 protein epitopes of in a murine model of invasive candidiasis.靶向侵袭性念珠菌病小鼠模型中细胞壁Pmt4蛋白表位的单克隆抗体的预防作用
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