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2R,3R-二氢杨梅素通过靶向 Sortase A 的抗生物膜机制及其在抑制鸡蛋壳表面金黄色葡萄球菌黏附中的应用。

Antibiofilm mechanism of 2R,3R-dihydromyricetin by targeting sortase A and its application against Staphylococcus aureus adhesion on eggshell.

机构信息

College of Biomass Science and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.

College of Biomass Science and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.

出版信息

Int J Food Microbiol. 2025 Jan 2;426:110925. doi: 10.1016/j.ijfoodmicro.2024.110925. Epub 2024 Sep 30.

DOI:10.1016/j.ijfoodmicro.2024.110925
PMID:39366090
Abstract

Biofilm formation of Staphylococcus aureus in food processing environments raises significant safety concerns, necessitating the development of new antibiofilm approaches for controlling S. aureus contamination. This study aimed to elucidate the antibiofilm mechanism of 2R,3R-dihydromyricetin (DMY), a natural flavonoid, against S. aureus and evaluate its efficacy in reducing bacterial adhesion to eggshell. The results revealed that DMY was a potent inhibitor of S. aureus sortase A (SrtA) with an IC of 73.43 μM, preventing bacterial adhesion to fibrinogen and subsequent biofilm formation. Fluorescence quenching assay and surface plasmon resonance analysis confirmed that DMY could directly bind to S. aureus SrtA. Notably, circular dichroism spectra demonstrated a conformational change in SrtA from α-helical to β-sheet structure upon DMY binding. Molecular dynamics simulation suggested that DMY bound to the catalytic pocket of S. aureus SrtA via hydrophobic interactions and hydrogen bonds. Furthermore, fluorescence microscopic observations further revealed that DMY attenuated the biofilm-related phenotype of SrtA by decreasing the anchoring of S. aureus protein A (SpA) onto cell wall. Importantly, pretreatment with 125 μg/mL DMY significantly reduced 1.14-1.75 log CFU/cm of S. aureus adhered on eggshells. Overall, these findings highlight how specific targeting of SrtA by DMY inhibits the attachment stages of biofilm development in S. aureus, making it a promising candidate for a novel disinfectant against this pathogen in the food industry.

摘要

金黄色葡萄球菌在食品加工环境中形成生物膜引起了重大的安全问题,因此需要开发新的抗生物膜方法来控制金黄色葡萄球菌的污染。本研究旨在阐明天然黄酮类化合物 2R,3R-二氢杨梅素(DMY)对金黄色葡萄球菌的抗生物膜机制,并评估其降低细菌黏附蛋壳的功效。结果表明,DMY 是一种有效的金黄色葡萄球菌表面蛋白 A(SrtA)抑制剂,IC 为 73.43 μM,可防止细菌黏附纤维蛋白原和随后的生物膜形成。荧光猝灭实验和表面等离子体共振分析证实 DMY 可直接与 S. aureus SrtA 结合。值得注意的是,圆二色谱表明 DMY 结合后 SrtA 的构象从α-螺旋变为β-折叠。分子动力学模拟表明,DMY 通过疏水相互作用和氢键结合到金黄色葡萄球菌 SrtA 的催化口袋中。此外,荧光显微镜观察进一步表明,DMY 通过减少金黄色葡萄球菌蛋白 A(SpA)与细胞壁的锚定,减弱了 SrtA 的生物膜相关表型。重要的是,用 125 μg/mL 的 DMY 预处理可显著减少 1.14-1.75 log CFU/cm 的金黄色葡萄球菌黏附在蛋壳上。总的来说,这些发现强调了 DMY 通过特异性靶向 SrtA 抑制金黄色葡萄球菌生物膜形成的附着阶段,使其成为食品工业中针对该病原体的新型消毒剂的有前途的候选物。

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