Senenic acid 28甲酯对耐甲氧西林金黄色葡萄球菌的抗菌活性
Antibacterial activity of Senegenic acid 28-methyl ester against methicillin-resistant Staphylococcus aureus.
摘要(中文译文)
耐甲氧西林金黄色葡萄球菌（MRSA）因其抗生素耐药性和生物膜形成能力而构成重大临床挑战。本研究对天然五环三萜类化合物进行筛选，以鉴定具有高抗菌活性的先导化合物。Senegenic acid 28-methyl ester（4）作为一种有效的抗MRSA及临床分离多重耐药菌株的抗菌剂，其最低抑菌浓度（MIC）为8–64 μg/mL。我们采用网络药理学预测化合物4的抗菌机制，并通过时间-杀菌试验和膜功能检测进行验证。结果表明，化合物4以剂量依赖性方式破坏细菌膜并抑制生物膜形成，降低生物量和胞外DNA水平。在体内，化合物4显著提高小鼠感染模型的存活率，同时表现出低细胞毒性和极低的溶血活性。此外，对 antibacterial 机制的深入研究通过分子对接和结构可视化分析发现，化合物4下调MRSA中关键生物膜相关基因（如sarA和atl）。非靶向代谢组学揭示，化合物4处理引起代谢物的广泛变化，并在氨基酸、能量和核苷酸代谢通路中显著富集。总体而言，这些发现确立化合物4作为一种兼具抗生物膜特性和调节细菌物质与能量代谢的双重作用剂，用于对抗MRSA感染。
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant clinical challenge owing to its antibiotic resistance and biofilm-forming ability. In this study, we conducted a screening of natural pentacyclic triterpenoids to identify lead compounds with high antibacterial activity. Senegenic acid 28-methyl ester (4) emerged as a potent antibacterial agent against MRSA and clinically isolated multidrug-resistant strains, with minimum inhibitory concentrations (MICs) of 8-64 μg/mL. We predicted the antibacterial mechanism of compound 4 using network pharmacology and validated by time-kill assays and membrane function tests. The results showed that compound 4 disrupted bacterial membranes and inhibited biofilm formation in a dose-dependent manner, reducing biomass and extracellular DNA levels. In vivo, compound 4 significantly improved survival in murine infection models, while demonstrating low cytotoxicity and minimal hemolytic activity. Furthermore, in-depth research on antibacterial mechanisms found that compound 4 downregulated key biofilm-associated genes (e.g., sarA and atl) in MRSA, which indicated by molecular docking and structural visualization analyses. Untargeted metabolomics revealed that compound 4 treatment induced widespread changes in metabolites and significant enrichment in amino acid, energy, and nucleotide metabolism pathways. Overall, these findings establish compound 4 as a dual-action agent with both anti-biofilm properties and regulate bacterial substance and energy metabolism against MRSA infections.
如何引用
AMA
Libang Zhang, Xingru Chen, Hao Wu, Weiwei Wang, Jian Zhang, Pingping Shen. Antibacterial activity of Senegenic acid 28-methyl ester against methicillin-resistant Staphylococcus aureus.. Bioorganic chemistry. 2026; doi:10.1016/j.bioorg.2026.110355.
APA
Libang Zhang, Xingru Chen, Hao Wu, Weiwei Wang, Jian Zhang, Pingping Shen (2026). Antibacterial activity of Senegenic acid 28-methyl ester against methicillin-resistant Staphylococcus aureus.. Bioorganic chemistry. https://doi.org/10.1016/j.bioorg.2026.110355
GB/T 7714
Libang Zhang, Xingru Chen, Hao Wu, Weiwei Wang, Jian Zhang, Pingping Shen. Antibacterial activity of Senegenic acid 28-methyl ester against methicillin-resistant Staphylococcus aureus.[J]. Bioorganic chemistry, 2026 doi:10.1016/j.bioorg.2026.110355.
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