关键词: Staphylococcus aureus antibacterial mechanisms fatty acid biosynthesis metabolomics quercetin transcriptomics β-ketoacyl-ACP reductase

Mesh : Quercetin / pharmacology chemistry Staphylococcus aureus / drug effects Fatty Acids / metabolism biosynthesis Anti-Bacterial Agents / pharmacology Molecular Docking Simulation Metabolomics / methods Transcriptome / drug effects Phytochemicals / pharmacology chemistry Gene Expression Profiling Cell Membrane / drug effects metabolism Gene Expression Regulation, Bacterial / drug effects Metabolome / drug effects Cell Membrane Permeability / drug effects

来  源:   DOI:10.3390/molecules29102266   PDF(Pubmed)

Abstract:
The utilization of natural products in food preservation represents a promising strategy for the dual benefits of controlling foodborne pathogens and enhancing the nutritional properties of foods. Among the phytonutrients, flavonoids have been shown to exert antibacterial effects by disrupting bacterial cell membrane functionality; however, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of quercetin on the cell membrane permeability of Staphylococcus aureus ATCC 27217. A combined metabolomic and transcriptomic approach was adopted to examine the regulatory mechanism of quercetin with respect to the fatty acid composition and associated genes. Kinetic analysis and molecular docking simulations were conducted to assess quercetin\'s inhibition of β-ketoacyl-acyl carrier protein reductase (FabG), a potential target in the bacterial fatty acid biosynthesis pathway. Metabolomic and transcriptomic results showed that quercetin increased the ratio of unsaturated to saturated fatty acids and the levels of membrane phospholipids. The bacteria reacted to quercetin-induced stress by attempting to enhance fatty acid biosynthesis; however, quercetin directly inhibited FabG activity, thereby disrupting bacterial fatty acid biosynthesis. These findings provide new insights into the mechanism of quercetin\'s effects on bacterial cell membranes and suggest potential applications for quercetin in bacterial inhibition.
摘要:
在食品保存中利用天然产品代表了控制食源性病原体和增强食品营养特性的双重益处的有希望的策略。在植物营养素中,类黄酮已被证明通过破坏细菌细胞膜功能发挥抗菌作用;然而,潜在的分子机制仍然难以捉摸。在这项研究中,我们研究了槲皮素对金黄色葡萄球菌ATCC27217细胞膜通透性的影响。采用代谢组学和转录组学相结合的方法来研究槲皮素在脂肪酸组成和相关基因方面的调节机制。进行动力学分析和分子对接模拟以评估槲皮素对β-酮脂酰-酰基载体蛋白还原酶(FabG)的抑制作用,细菌脂肪酸生物合成途径中的潜在靶标。代谢组学和转录组学结果表明,槲皮素增加了不饱和脂肪酸与饱和脂肪酸的比例和膜磷脂的水平。该细菌通过试图增强脂肪酸的生物合成来对槲皮素诱导的应激做出反应;然而,槲皮素直接抑制FabG活性,从而破坏细菌脂肪酸的生物合成。这些发现为槲皮素对细菌细胞膜的作用机制提供了新的见解,并提示了槲皮素在细菌抑制中的潜在应用。
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