孙培培;张宁;赵琳静;彭媛媛;刘锡建;刘晓会;翟亚森;冯美卿;

• 1:上海工程技术大学化学化工学院
• 2:复旦大学药学院

摘要(Abstract)：

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_1Cer)、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。

关键词(KeyWords)： 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

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(No.31701032)资助~~

作者(Authors): 孙培培;张宁;赵琳静;彭媛媛;刘锡建;刘晓会;翟亚森;冯美卿;

DOI: 10.19756/j.issn.0253-3820.210716

参考文献(References)：

• [1] SEGAWA K,NAGATA S.Trends Cell Biol.,2015,25(11):639-650.
• [2] VARTABEDIAN V F,SAVAGE P B,TEYTON L.Immunol.Rev.,2016,272(1):109-119.
• [3] SINGH A,KHANDELWAL N K,PRASAD R.Prog.Mol.Subcell.Biol.,2019,58:195-215.
• [4] ALFATAH M,BARI V K,NAHAR A S,BIJLANI S,GANESAN K.Sci.Rep.,2017,7:40281.
• [5] HAN X,GROSS R W.J.Lipid Res.,2003,44(6):1071-1079.
• [6] HAN X.Nat.Rev.Endocrinol.,2016,12(11):668-679.
• [7] MIRZA ALIZADEH A,GOLZAN S A,MAHDAVI A,DAKHILI S,TORKI Z,HOSSEINI H.Crit.Rev.Food Sci.Nutr.,2021:1878102.
• [8] FARISA BANU S,RUBINI D,SHANMUGAVELAN P,MURUGAN R,GOWRISHANKAR S,KARUTHA PANDIAN S,NITHYANAND P.J.Mycol.Med.,2018,28(2):332-339.
• [9] ESSID R,HAMMAMI M,GHARBI D,KARKOUCH I,HAMOUDA T B,ELKAHOUI S,LIMAM F,TABBENE O.Appl.Microbiol.Biotechnol.,2017,101(18):6993-7006.
• [10] GOEL N,ROHILLA H,SINGH G,PUNIA P.J.Clin.Diagn.Res.,2016,10(8):DC09-DC11.
• [11] EL-BAZ A M,MOSBAH R A,GODA R M,MANSOUR B,SULTANA T,DAHMS T E S,EL-GANINY A M.Antibiotics (Basel).,2021,10(1):81.
• [12] DE ALMEIDA L D D,DE PAULA J F,DE ALMEIDA R V D,WILLIAMS D W,HEBLING J,CAVALCANTI Y W.Acta Odontol.Scand.,2016,74(5):393-398.
• [13] YAN H,QIAN G Y,YANG R,LUO Z C,WANG X Z,XIE T,ZHAO X,SHAN J J.Front.Pharmacol.,2021,12:656756.
• [14] ZHANG Miao-Miao,GUO Xiao-Peng,LIU Rui-Yuan,MA Liang,GAO Yue,LU Dong,LI Wen-Jian.Chin.J.Anal.Chem.,2018,46(11):1714-1723.张苗苗，郭晓鹏，刘瑞媛，马良，高越，陆栋，李文建.分析化学，2018,46(11):1714-1723.
• [15] NCCLS,1975.Performance Standards for Antimicrobial Disc Susceptibility Tests Approved Standard M2-A2.National Committee for Clinical Laboratory Standards,Villanova,Pennsylvania,1979.
• [16] CLSI,2008.Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts;Approved Standard M27-A3,3rd Edn.Wayne,PA.
• [17] CALVANO C D,MONOPOLI A,DITARANTO N,PALMISANO F.Anal.Chim.Acta,2013,798:56-63.
• [18] CALDERóN C,SANWALD C,SCHLOTTERBECK J,DROTLEFF B,L?MMERHOFER M.Anal.Chim.Acta,2019,1048:66-74.
• [19] MATYASH V,LIEBISCH G,KURZCHALIA T V,SHEVCHENKO A,SCHWUDKE D.J.Lipid Res.,2008,49(5):1137-1146.
• [20] BENJAMINI Y,HOCHBERG Y.J.R.Stat.Soc.Series.B.Stat.Methodol.,1995,57:289-300.
• [21] ZHAO L J,NI Y,SU M M,LI H S,DONG F C,CHEN W L,WEI R M,ZHANG L L,GUIRAUD S P,MARTIN F P,RAJANI C,XIE G X,JIA W.Anal.Chem.,2017,89(10):5565-5577.
• [22] VAN MEER G,VOELKER D R,FEIGENSON G W.Nat.Rev.Mol.Cell Biol.,2008,9(2):112-124.
• [23] CAJKA T,SMILOWITZ J T,FIEHN O.Anal.Chem.,2017,89(22):12360-12368.
• [24] DA SILVA K M,ITURROSPE E,HEYRMAN J,KOELMEL J P,CUYKX M,VANHAECKE T,COVACI A,VAN NUIJS A L N.Talanta,2021,235:122808.
• [25] HANS S,FATIMA Z,HAMEED S.J.Appl.Microbiol.,2021,doi:10.1111/jam.15265.
• [26] CASSILLY C D,FARMER A T,MONTEDONICO A E,SMITH T K,CAMPAGNA S R,REYNOLDS T B.FEMS Yeast.Res.,2017,17(2):fox007.
• [27] HOLTHUIS J C,MENON A K.Nature,2014,510(7503):48-57.
• [28] GIBELLINI F,SMITH T K.IUBMB Life,2010,62(6):414-428.
• [29] JAIN S,ZHANG X,KHANDELWAL P J,SAUNDERS A J,CUMMINGS B S,OELKERS P.J.Lipid Res.,2009,50(8):1563-1570.
• [30] CHEN Y L,MONTEDONICO A E,KAUFFMAN S,DUNLAP J R,MENN F M,REYNOLDS T B.Mol.Microbiol.,2010,75(5):1112-1132.
• [31] KHANDELWAL N K,SARKAR P,GAUR N A,CHATTOPADHYAY A,PRASAD R.Biochim.Biophys.Acta Biomembr.,2018,1860(11):2308-2319.
• [32] SCHLAME M,RUA D,GREENBERG M L.Prog.Lipid Res.,2000,39(3):257-288.
• [33] MOTA FERNANDES C,DEL POETA M.Expert.Rev.Anti-Infect.Ther.,2020,18(11):1083-1092.
• [34] MCEVOY K,NORMILE T G,POETA M D.J.Fungi (Basel),2020,6(3):142.
• [35] ALQAISI A Q I,MBEKEANI A J,LLORENS M B,ELHAMMER A P,DENNY P W.Parasitology,2018,145(2):148-155.
• [36] SHARMA M,DHAMGAYE S,SINGH A,PRASAD R.Front.Biosci.,2012,4:1195-1209.
• [37] FATIMA Z,HAMEED S.Infect.Disord.Drug Targets,2020,20(6):784-797.