目的：阐释三七（Panax notoginseng, PN）对耐甲氧西林金黄色葡萄球菌（Methicillin-resistant Staphylococcus aureus, MRSA）菌株 ATCC43300（医院获得性）和 USA300（社区获得性）的药效差异及分子机制。方法：采用RNA-Seq技术分析PN干预对两株MRSA转录组的影响，以|log?FC|≥1.0且FDR<0.05为筛选标准，鉴定差异表达基因（DEGs）。进一步结合Gene Ontology（GO）和Kyoto Encyclopedia of Genes and Genomes（KEGG）功能富集分析、加权基因共表达网络分析（WGCNA）及蛋白质互作网络（PPI）分析，识别相关的关键通路与核心调控基因。结果：在ATCC43300中，共鉴定出478个差异表达基因，其中上调基因201个，下调基因277个；在USA300中，鉴定出274个差异表达基因，其中上调基因130个，下调基因144个。ATCC43300中，支链氨基酸代谢和膜脂代谢通路显著上调；而在USA300中，嘌呤代谢和群体感应通路显著下调。WGCNA分析识别出与PN干预相关的核心模块，ATCC43300的核心模块富集在膜脂代谢相关基因，而USA300则富集在氨基酸代谢通路。PPI分析揭示，ATCC43300中与膜脂代谢和氧化还原相关的多个通路受到影响，而USA300中，嘌呤代谢与群体感应系统相关的多个基因通路受到抑制，表明PN可能通过干扰这些关键代谢和信号通路，削弱细菌的致病能力。 结论：PN可诱导MRSA菌株的多个代谢通路变化，表现出对不同菌株的代谢重构效应。ATCC43300中，支链氨基酸代谢与膜脂合成通路显著上调，可能通过增强代谢负担和氧化应激反应，干扰其膜结构稳定性与代谢稳态，从而削弱其生存适应性并影响耐药相关功能通路。USA300中，嘌呤代谢与群体感应系统显著下调，推测PN可通过抑制毒力因子表达削弱其致病能力。本研究揭示了PN对MRSA菌株的差异化转录调控机制，为其在不同MRSA菌株感染中的精准应用提供理论依据。

Objective To elucidate the differential antibacterial effects and underlying molecular mechanisms of Panax notoginseng (PN) against methicillin-resistant Staphylococcus aureus (MRSA) strains ATCC43300 (hospital-associated) and USA300 (community-associated). Methods Transcriptomic changes in the two MRSA strains upon PN treatment were analyzed using RNA sequencing (RNA-Seq). Differentially expressed genes (DEGs) were identified based on the criteria of |log?FC| ≥ 1.0 and false discovery rate (FDR) < 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, weighted gene co-expression network analysis (WGCNA), and protein–protein interaction (PPI) network analysis were performed to identify key pathways and core regulatory genes. Results A total of 478 and 274 differentially expressed genes (DEGs) were identified in ATCC43300 and USA300, respectively. In ATCC43300, branched-chain amino acid metabolism and glycerophospholipid metabolism pathways were significantly upregulated, whereas in USA300, purine metabolism and quorum sensing pathways were notably downregulated. WGCNA revealed PN-associated core modules, with ATCC43300 enriched in lipid metabolism-related genes and USA300 in amino acid metabolism pathways. PPI network analysis showed key interactions between multiple pathways related to lipid metabolism and redox processes in ATCC43300, and between multiple pathways associated with purine metabolism and quorum sensing in USA300. These findings suggest that PN may weaken the pathogenicity of MRSA by interfering with these key metabolic and signaling pathways. Conclusion PN induces alterations in multiple metabolic pathways in MRSA strains, exhibiting strain-specific metabolic reprogramming effects. In ATCC43300, the significant upregulation of branched-chain amino acid metabolism and lipid biosynthesis pathways may increase metabolic burden and oxidative stress, disrupting membrane stability and metabolic homeostasis, ultimately reducing bacterial adaptability and affecting resistance-related functional pathways. In USA300, the significant downregulation of purine metabolism and quorum sensing system suggests that PN may attenuate virulence by suppressing toxin gene expression. This study reveals the differential transcriptomic regulatory mechanisms of PN in MRSA strains and provides theoretical support for its strain-specific application in the treatment of MRSA infections.

]中国中医科学院科技创新工程中医临床基础学科创新团队项目(No.C2021B003)；中国中医科学院自主选题项目(No.Z0735)