Membrane-targeted mechanism for amphiphilic vitamin C compounds as methicillin-resistant Staphylococcus aureus biofilm eradicating agents

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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Abstract

Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. The extensive use of disinfectants against biofilms has led to negative environmental impacts. Developing new and more potent biofilm eradication agents with minimal detrimental effects on human and environmental health is currently on the agenda. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are able to kill the persister cells of the deepest layers of the biofilm. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.

两亲性维生素 C 复合物作为耐甲氧西林金黄色葡萄球菌生物膜根除剂的膜靶机制。
金黄色葡萄球菌感染及其生物膜的清除是医疗保健管理中的一个重要问题。耐甲氧西林金黄色葡萄球菌在全球范围内造成了严重的发病率和死亡率。针对生物膜的消毒剂的广泛使用导致了对环境的负面影响。目前,开发新的、对人类和环境健康影响最小的、更有效的生物膜根除剂已提上议事日程。左旋抗坏血酸烷基酯(ASCn)是一种抗氧化双亲化合物,对甲氧西林敏感和耐药金黄色葡萄球菌菌株具有抗菌能力。ASC12 和 ASC14 配方能够杀死生物膜最深层的顽固细胞。我们测试了一个假设,即 ASCn 的抗菌和抗生物膜能力来自其两亲性和氧化还原能力的共同作用。这一机制似乎与以下方面有关I)与 ASC14 和 ASC16 微结构相比,ASC12 胶束的扩散能力更大;II)当两亲性物质到达阴离子表面时,ASCn 酸羟基被中和,然后迅速插入;III)通过改变膜张力和结构破坏细胞膜;IV)ASCn 在细胞膜或生物膜细胞外基质表面积聚,减少功能化学基团,影响其生物功能。
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来源期刊
Chemistry and Physics of Lipids
Chemistry and Physics of Lipids 生物-生化与分子生物学
CiteScore
7.60
自引率
2.90%
发文量
50
审稿时长
40 days
期刊介绍: Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.
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