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胆酸衍生两亲物可预防和降解真菌生物膜。

Cholic-Acid-Derived Amphiphiles Can Prevent and Degrade Fungal Biofilms.

机构信息

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, Third Milestone Faridabad-Gurgaon Expressway, NCR Biotech Science Cluster, Faridabad 121001, Haryana, India.

Department of Chemistry, Indian Institute of Science Education and Research, Bhopal 462066, Madhya Pradesh, India.

出版信息

ACS Appl Bio Mater. 2021 Sep 20;4(9):7332-7341. doi: 10.1021/acsabm.9b01221. Epub 2020 Mar 20.

Abstract

Infections caused by fungal species via their existence as biofilms on medical devices can cause organ damage via candidiasis and candidemia. Different species like can pose a serious threat by resisting host's immune system and by developing drug resistance against existing antimycotic agents. Therefore, targeting of fungal membranes can be used as an alternative strategy to combat the fungal infections. Here, we present screening of different amphiphiles based on cholic acid against different strains as these amphiphiles can act as potent membrane-targeting antimycotic agents. Structure-activity correlations, biochemical assays and electron microscopy studies showed that amphiphiles having and carbon chains are most potent, safe and can act on the fungal membranes. did not show emergence of drug resistance on repeated usage of these amphiphiles unlike fluconazole. We show that these amphiphiles can prevent the formation of biofilms and also have the ability to degrade preformed biofilms on different substrates including acrylic teeth. We further demonstrate that amphiphiles and can clear the wound infections and prevent the biofilm formation on indwelling devices in murine models. Therefore, amphiphiles derived from cholic acid and their coatings provide suitable alternatives for inhibiting the fungal infections.

摘要

真菌物种通过在医疗器械上形成生物膜而引起的感染会导致念珠菌病和念珠菌血症引起的器官损伤。不同的物种,如 ,可以通过抵抗宿主的免疫系统和对现有抗真菌药物产生耐药性来构成严重威胁。因此,靶向真菌膜可以作为对抗真菌感染的一种替代策略。在这里,我们基于胆酸对不同 株进行了不同两亲分子的筛选,因为这些两亲分子可以作为有效的膜靶向抗真菌剂。结构-活性关系、生化分析和电子显微镜研究表明,具有 和 个碳原子的两亲分子是最有效、最安全的,可以作用于真菌膜。与氟康唑不同,这些两亲分子在反复使用后不会产生耐药性。我们表明,这些两亲分子可以防止生物膜的形成,并且还具有在包括丙烯酸牙齿在内的不同基质上降解已形成的生物膜的能力。我们进一步证明,两亲分子 和 可以清除 伤口感染,并防止在小鼠模型中留置装置上形成生物膜。因此,胆酸衍生的两亲分子及其涂层为抑制真菌感染提供了合适的替代品。

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