抗MRSA植物药组方MZL-1的药效作用及分子机制

Inhibitory effect and molecular mechanism of medicinal plants formula MZL-1 against MRSA

以耐甲氧西林金黄色葡萄球菌(Methicillin-resistant Staphylococcus aureus,MRSA)为研究对象,对实验室研发的植物药组方MZL-1进行抗MRSA药效作用及分子机制研究。采用倍比稀释法测定MZL-1的抑菌效果,检测相对电导率、碱性磷酸酶活性变化,分析MZL-1对MRSA菌体细胞壁、细胞膜的破坏和完整性的影响,测定组方处理对MRSA细胞的促凋亡作用,并对MZL-1抗菌的可能分子作用机制进行探究。结果表明:MZL-1对MRSA的MIC(Minimal inhibit concentration)为7.5%,MZL-1处理后,MRSA菌液电导率和碱性磷酸酶活性显著增高;扫描电镜观察细胞形态差异变化大并受损,表明MZL-1破坏了MRSA细胞的完整性,导致内容物溢出,大量细胞凋亡且多出现在早期阶段;网络药理学分析发现29个化合物和23个靶基因,其中,RELA可能是核心靶基因;Gene Ontology(GO)富集分析显示靶基因主要参与细胞对小分子反应,细胞因子及转录因子等过程;Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析发现所涉及的通路主要集中在炎症反应、细胞凋亡、免疫功能及细菌和病毒感染等。研究认为组方MZL-1有望研发成为抗MRSA等耐药病原菌以及微生物感染的潜在植物源类药物。

Methicillin-resistant Staphylococcus aureus(MRSA)was used to study the anti-MRSA effect and preliminary molecular mechanism of the medicinal plant formula MZL-1 developed in the laboratory.The antibacterial effect of MZL-1 was confirmed by the double dilution method,and the relative conductivity,alkaline phosphatase activity change and scanning electron microscope observation were detected to analyze the effect of MZL-1 treatment on the destruction and integrity of the cell wall and membrane of MRSA.Flow cytometry was utilized to determine the effect of MZL-1 on MRSA for cell apoptosis.Network pharmacology was applied to explore the possible molecular mechanism of the anti-microbial effects of MZL-1.The result showed that the MIC of MZL-1 to MRSA was 7.5%.The increase in the activities of relative electric conductivity and alkaline phosphatase as well as the significant changes in morphology and damages observed by scanning electron microscopy indicated that MZL-1 obviously disrupted the integrity of MRSA cells and hence caused the overflow of the cell contents.Flow cytometry analysis found that a large number of cell apoptosis occurred in the early stage.Network pharmacology discovered 29 compounds and 23 target genes for MZL-1 in anti-microbial infection,and RELA may be the core gene.Gene Ontology(GO)enrichment analysis showed that target genes were mainly involved in the cell’s response to small molecules,cytokines and transcription factors.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis found that the pathways involved mainly focused on inflammation,apoptosis,immune function,and bacterial and viral infections.Based on the current research,the formula MZL-1 might be potentially developed to be a plant-derived drug against MRSA and other drug-resistant pathogens and microbial infections.