光滑念珠菌氟康唑耐药株与敏感株比较蛋白质组研究.pdfVIP

光滑念珠菌氟康唑耐药株与敏感株比较蛋白质组研究 沈银忠 张丽军 贾小芳 卢洪洲 张永信* 1.上海市公共卫生临床中心，上海2015082.复旦大学附属华山医院，上海200040 摘要：目的 从蛋白质水平研究光滑念珠菌的耐药机制，为发现和研究新的耐药相关基因及机制提供理论和 实验基础。方法 采用比较蛋白质组研究技术比较光滑念珠菌氟康唑耐药株和敏感株蛋白质组的差异。结 果 发现12种差异表达蛋白质，其中8种在耐药株中表达上调，4种在敏感株中表达上调。这些差异蛋白 质属于能量代谢相关酶类、应激反应蛋白质及大分子合成相关蛋白质等。结论 能量代谢相关酶类、应激 反应蛋白质及大分子合成相关蛋白质等均有可能参与了光滑念珠菌耐药性的形成过程，光滑念珠菌耐药性 的形成是多种机制共同作用的结果，上述差异蛋白质的发现为进一步研究新的耐药相关基因和耐药机制提 供了理论基础。 关键词：光滑念珠菌；氟康唑；耐药性；比较蛋白质组学 Comparativeproteomieanalysisoffluconazole-resistantandfluconazole-sensitiveCandida glabrataisolates SHENYin-zhongZHANGLi-junJIAXiao-fangLUHong-zhouZhangYong-xin DepartmentofInfectiousDiseases,ShanghaiPublicHealthClinicalCenter,FudanUniversity,Shanghai201508; HuashanHospital, FudanUniversity,Shanghai200040 ABSTRACT:Objective TheknownmolecularmechanismsoffluconazoleresisitanceinCandidaglabrataare notsufficienttoexplaintheresistanceinclinicalisolatesofC.glabrata,newresistance-associatedgenesandother possibleunderlyingresistancemechanismsdeserveagreatdealofconcernandinvestigation.Methods Weused proteomics-associatedtechniquestoidentifychangesintheproteomeoffluconazole-resistantisolatesofC. glabratacomparedwithfluconazole-sensitiveonesinordertoidentifyproteinsthataredifferentiallyexpressedin associatedwithfluconazoleresistance.Results Eightproteinswerefoundtobemoreabundantlyrepresented, andfourproteinswerefoundtobelessabundantlyrepresented,influconazole-resistantstrainscomparedwith fluconazole-sensitiveones.Thesedifferentiallyexpressedproteinsinvolvedinenergymetabolism,stressresponse andmacromoleculesynthesis.Conclusions Theseresultsindicatethatproteinsinvolvedinenergymetabolism, stressresponseandmacromoleculesynthesismayplayaroleinthedevelopmentoffluconazoleresistancein clinicalisolatesofC.glabrata.Thestudyprovidesfurtherevidencethatmanydifferentmechanismsareinvolved inthedevelopmentoffluconazoleresistan