亚抑菌浓度肉桂挥发油暴露对白色念珠菌脂质稳态的影响  

Effects of Cinnamon Oil at Subinhibitory Concentration on Lipid Homeostasis of Candida Albicans

作　　者：孙培培 张宁 赵琳静[1] 彭媛媛 刘锡建[1] 刘晓会[1] 翟亚森 冯美卿[2] SUN Pei-Pei;ZHANG Ning;ZHAO Lin-Jing;PENG Yuan-Yuan;LIU Xi-Jian;LIU Xiao-Hui;ZHAI Ya-Sen;FENG Mei-Qing(School of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620,China;School of Pharmacy,Fudan University,Shanghai 201203,China)

机构地区：[1]上海工程技术大学化学化工学院,上海201620 [2]复旦大学药学院,上海201203

出　　处：《分析化学》2022年第1期92-102,I0001-I0005,共16页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(No.31701032)资助。

摘　　要：肉桂挥发油(Cinnamon oil,CO)对念珠菌属(Candida spp.)真菌的生长有良好的抑制作用。本研究采用传统微生物学方法和基于超高效液相色谱-四极杆-静电场轨道阱质谱(UPLC-QE-MS)的高覆盖性脂质组学(High-coverage lipidomics)技术,结合多维及单变量统计分析方法,研究亚抑菌浓度(0.1×MIC)肉桂挥发油对白色念珠菌(Candida albicans,C.albicans)细胞形态和脂质稳态的影响,并挖掘显著性差异脂质分子之间的共调控网络关系。结果表明,亚抑菌浓度肉桂挥发油可使对数生长中期的C.albicans细胞形态发生明显改变。采用脂质组学分析,从C.albicans细胞中共鉴定出脂质分子1281种,涉及6大类45亚类脂质;通过正交偏最小二乘判别分析(OPLS-DA)的变量权重值、非参检验及变异倍数分析,共筛选出55种显著性差异脂质代谢标志物,主要包括磷脂酰乙醇胺(Phosphatidylethanolamine,PE)及其衍生物二甲基磷脂酰乙醇胺(Dimethylphosphatidylethanolamine,dMePE)、磷脂酰胆碱(Phosphatidylcholine,PC)、磷酯酰丝氨酸(Phosphatidylserine,PS)、磷脂酰甘油(Phosphatidylglycerol,PG)、心磷脂(Cardiolipin,CL)、磷脂酰肌醇(Phosphatidylinositol,PI)、神经酰胺(Ceramide,Cer)及其衍生物己糖基神经酰胺(Hexosyl ceramide,Hex_(1) Cer)、甘油三酯(Triglyceride,TG)、甘油二酯(Diglyceride,DG)等共15个亚类;除PI等5种脂质外,其余脂质分子在肉桂挥发油暴露压力下均显著下调。采用层次聚类分析和相关分析,初步分析了显著性差异脂质分子(r>0.8,p<0.05)间的相互作用网络。结果表明,肉桂挥发油对C.albicans生长抑制作用与影响细胞膜和线粒体的正常代谢功能有关,发现的显著性差异脂质可能是其抑制C.albicans生长的潜在代谢标记物。Cinnamon oil(CO)shows a good antifungal activity against Candida Spp.However,the mechanism remains unclear,especially from the metabolic perspective.In this study,the effects of CO at subinhibitory concentration on Candida albicans were investigated by traditional microbiological method and measurement of lipids profile using a high-coverage lipidomics based on ultra-performance liquid chromatography-Q exactive-mass spectrometry(UPLC-QE-MS),combined with multivariate and univariate data statistical analyses.The results showed that the cell morphology of C.albicans was obviously changed when exposure to CO at subinhibitory concentration(0.1×MIC).A total of 1281 lipids species were identified in cells of C.albicans,which belong to 45 classes in 6 categories.Among them,55 lipid species were significantly altered under CO treatment,mainly involving 15 lipids classes such as phosphatidylethanolamine(PE)and the derivative dimethylphosphatidylethanolamine(dMePE),phosphatidylcholine(PC),phosphatidylserine(PS),phosphatidylglycerol(PG),cardiolipin(CL),phosphatidylinositol(PI),ceramide(Cer)and the derivative hexosyl ceramide(Hex_(1)Cer),triglyceride(TG),diglyceride(DG),etc.All but five lipid species were significantly down-regulated response to CO-treated treatment.The interaction network between the key lipid species with r>0.8 and p<0.05 was constructed by using hierarchical clustering analysis and correlation analysis.This study suggested that the antifungal effect of CO on C.albicans was potentially associated with the injured metabolic functions of cell membrane and mitochondria.The lipid species with significant difference expression level may be potentially metabolic markers for the inhibitory effect of CO against C.albicans.

关 键 词：脂质组学 代谢响应 肉桂挥发油 白色念珠菌 超高效液相色谱-四极杆-静电场轨道阱质谱 

分 类 号：O657.63[理学—分析化学] TQ460.1[理学—化学]