一株临床耐氟康唑白念珠菌生物膜特性及耐药相关基因表达的初步研究

发布时间：2018-06-13 08:51

本文选题：白念珠菌 + 氟康唑　；参考：《现代预防医学》2017年15期

【摘要】：目的探讨一株临床耐氟康唑白念珠菌生物膜特性及可能的耐药机制。方法选取临床分离的15株氟康唑敏感白念珠菌和1株耐氟康唑的白念珠菌,通过体外建膜比较各菌株产膜能力,荧光染色观察生物膜的生长。并利用qRT-PCR检测生物膜形成及耐药相关基因HWP1、ALS3、ERG11、MDR、CDR1及CMP1等在不同处理组中表达水平的变化。结果这株临床耐氟康唑白念珠菌产膜能力为中等;qRT-PCR检测显示,耐药菌株生物膜形成相关基因HWP1、ALS3相较于临床氟康唑敏感株均有不同程度的降低,而耐药相关基因ERG11、CDR1和CMP1表达量明显高于敏感菌株;当氟康唑和环胞菌素A联合处理耐药菌株后,该耐药菌株的耐药相关基因ERG11、CMP1、MDR和CDR1表达量与单独使用氟康唑时相比均有不同程度的降低,差异具有统计学意义(P0.05)。结论生物膜的形成可能不是该临床耐氟康唑白念珠菌产生耐药性的主要因素,其主要机制可能是通过药物靶酶基因ERG11,外排泵基因CDR1和钙调神经磷酸酶基因CMP1的过度表达实现的,而环胞菌素A能够通过降低药物靶酶和外排泵基因的表达增强这株耐氟康唑白念珠菌对氟康唑的敏感性。
[Abstract]:Objective to investigate the biofilm characteristics of a clinical fluconazole-resistant Candida albicans strain and its possible drug resistance mechanism. Methods 15 strains of fluconazole-sensitive Candida albicans and 1 strain of fluconazole-resistant Candida albicans were selected. The membrane production ability of each strain was compared by in vitro membrane building and the growth of biofilm was observed by fluorescence staining. The expression of biofilm formation and drug resistance related gene HWP1A1ALS3ERG11ERG11MDRnCDR1 and CMP 1 in different treatment groups were detected by qRT-PCR. Results the membrane production ability of fluconazole-resistant Candida albicans strain was moderate by qRT-PCR. The biofilm-forming related gene HWP1-ALS3 was lower than that of fluconazole-sensitive strain in different degree. When fluconazole and cyclosporine A combined with fluconazole and cyclosporin A, the expression of ERG11 gene CDR1 and CMP 1 was significantly higher than that of sensitive strain. The MDR and CDR1 expression levels of the resistant gene ERG11 ~ (1) CMP 1 were significantly lower than those of fluconazole alone, and the difference was statistically significant (P 0.05). Conclusion the formation of biofilm may not be the main factor of resistance to fluconazole-resistant Candida albicans, and its main mechanism may be the overexpression of drug target enzyme gene ERG11, efflux pump gene CDR1 and calmodulin phosphatase gene (CMP 1). Cyclosporin A could increase the sensitivity of fluconazole-resistant Candida albicans to fluconazole by reducing the expression of drug target enzyme and efflux pump gene.
【作者单位】：宁夏医科大学临床医学院;宁夏医学病原微生物重点实验室;宁夏医科大学总医院医学实验中心;
【基金】：宁夏临床病原微生物重点实验室开放课题(2015,LCPM201501-1) 2015年宁夏研究生教育创新计划项目(2016,NXYC201511)
【分类号】：R446.5

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