补骨脂二氢黄酮甲醚对耐甲氧西林金葡菌葡萄黄素的抑制作用  被引量:4

Inhibitory effect of bavachinin on methicillin-resistant Staphylococcus aureus staphyloxanthin

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作  者:丁颖 朱先鹏 李江波 刘爽 于清平 王琳 DING Ying;ZHU Xianpeng;LI Jiangbo;LIU Shuang;YU Qingping;WANG Lin(Ministry of Education Key Laboratory for Zoonotic Diseases/College of Veterinary Medicine,Jilin University,Changchun 130062,China;Jinziyuan Biological Technology Co.,Ltd.,of Jilin,Siping,Jilin 136400,China;Agriculture,Forestry and Water Conservancy of Xi'an District of Liaoyuan City,Liaoyuan,Jilin 136200,China;Agricultural Comprehensive Administrative Law Enforcement Brigade of Liuhe County,Liuhe,Jilin 135300,China;Agricultural Comprehensive Administrative Law Enforcement Brigade of Tonghua County,Tonghua,Jilin 134100,China)

机构地区:[1]吉林大学动物医学学院/人兽共患病研究教育部重点实验室,吉林长春130062 [2]吉林金梓源生物科技有限公司,吉林四平136400 [3]吉林省辽源市西安区农林水利工程总站,吉林辽源136200 [4]吉林省柳河县农业综合行政执法大队,吉林通化135300 [5]吉林省通化县农业综合行政执法大队,吉林通化134100

出  处:《中国兽医学报》2022年第12期2514-2521,共8页Chinese Journal of Veterinary Science

基  金:国家自然科学基金国际(地区)合作与交流资助项目(81861138046)。

摘  要:用葡萄黄素(staphyloxanthin,STX)抑制试验筛选药物并经高效液相色谱分析抑制STX的有效成分,经微量肉汤稀释法(MIC)和生长曲线测定评价药物对耐甲氧西林金黄色葡萄球菌(multidrug-resistant S.aureus,MRSA)生长的影响,通过氧敏感性试验和酸碱胁迫试验验证药物在体外对S.aureus毒力的影响,并通过黏附试验进一步验证,通过实时荧光定量PCR(RT-PCR)在转录水平对药物作用机制进行探讨。结果显示,补骨脂醇提物具有显著的STX抑制作用,对提取物中的主要成分进行分析,其中补骨脂二氢黄酮甲醚在较低质量浓度即可显著抑制STX的生成(IC_(50)=0.529 mg/L);补骨脂二氢黄酮甲醚呈剂量依赖性增强MRSA菌株USA300对过氧化氢的氧敏感性及降低其在酸碱胁迫环境中的存活率;补骨脂二氢黄酮甲醚能够抑制USA300对A549细胞的黏附作用,在细胞水平上验证了补骨脂二氢黄酮甲醚通过抑制STX降低了S.aureus的致病力;最后通过RT-PCR发现补骨脂二氢黄酮甲醚处理后USA300菌株STX生成途径及上游途径的6种基因表达均受到抑制。结果表明,补骨脂二氢黄酮甲醚可以通过抑制STX的合成降低MRSA的毒力,为治疗耐药S.aureus感染药物的开发提供了新的研究思路。Staphyloxanthin(STX)secreted by Staph ylococcus aureus(S.aureus),it is an important virulence factor of S.aureus,it can protect pathogens from being killed by oxidants and evade the immune clearance of the host.In this research,STX was used as a target for drug development in the treatment of multidrug-resistant S.aureus infection.In this study,the STX inhibition test was used to screen the drugs,and the effective components that inhibited STX were analyzed by high performance liquid chromatography(HPLC).The effects of drugs on the virulence of S.aureus in vitro were verified by oxygen sensitivity experiments and acid-base stress experiments.The experimental results were verified by adhesion assay,and the mechanism of drug action was explored at the transcriptional level by real-time PCR(RT-PCR).It was found that the psoralea methanol extract had a significant inhibitory effect on STX through the inhibition of STX production and MIC(minimum inhibitory concentration)experiments.Subsequently,the main components in the extract were analyzed.Among them,bavachinin was found that it could significantly inhibit the production of STX at a lower concentration(IC_(50)=0.529 mg/L)furthermore,it was demonstrated that bavachinin could dose-dependently enhance the oxygen sensitivity of MRSA strain USA300 to hydrogen peroxide and attenuate its survival in acid-base stress environment.Next,we found that bavachinin could inhibit the adhesion of USA300 to A549 cells,which verified that bavachinin reduced the pathogenicity of S.aureus by inhibiting STX at the cellular level.Finally,the results of RT-PCR experiments showed that the expression of six genes in the STX synthesis pathway and upstream pathway of USA300 strain were inhibited by treatment with bavachinin.This study demonstrates that bavachinin can reduce the virulence of MRSA by inhibiting the synthesis of STX,and provides a new research idea for the development of drugs for the treatment of drug-resistant S.aureus infections.Research on natural small molecule drugs as lea

关 键 词:补骨脂二氢黄酮甲醚 耐甲氧西林金葡菌 葡萄黄素抑制剂 

分 类 号:S852.61[农业科学—基础兽医学] S855.9[农业科学—兽医学]

 

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