新生隐球菌生物膜的构建、影响因素及耐药性的研究

发布时间：2019-06-10 12:55

【摘要】： [背景]生物膜可明显降低抗真菌药物的敏感性,目前有关隐球菌生物膜的构建及其耐药性的研究国内报道尚无。[目的]证实隐球菌生物膜的存在,探讨隐球菌生物膜在隐球菌耐药机制中的作用。[方法]构建隐球菌生物膜体外、动物模型并观察其超微结构和生长动力学;观察分析隐球菌生物膜形成的影响因素;研究新生隐球菌生物膜体外抗真菌药物敏感性。[结果]隐球菌生物膜体外、动物模型显示成熟的隐球菌生物膜呈一个有机的三维结构,典型的微菌落/水通道构象;隐球菌生物膜生长活性随培养时间延长而明显增强,达到一定成熟度后逐渐稳定;血清A型新生隐球菌比B型形成生物膜的能力强;脑脊液、血清预处理的隐球菌形成的生物膜厚度和活力均增强;生物膜状态下的新生隐球菌对各种抗真菌药耐药性增强。[结论]证实了隐球菌生物膜的存在;成熟的隐球菌生物膜呈一个有机的三维结构;隐球菌生物膜生长活性随培养时间延长而明显增强,达到一定成熟度后逐渐稳定;不同血清型的新生隐球菌可能形成生物膜的能力不同;脑脊液和血清对隐球菌生物膜的形成均有促进作用;生物膜状态下的新生隐球菌对各种抗真菌药敏感性明显降低,耐药性增强。
[Abstract]:[background] Biofilm can significantly reduce the sensitivity of antifungal drugs, but there is no domestic report on the construction of Cryptococcus biofilm and its drug resistance. [objective] to confirm the existence of Cryptococcus biofilm and to explore the role of Cryptococcus biofilm in the mechanism of drug resistance of Cryptococcus. [methods] Cryptococcus biofilm was constructed in vitro and its ultrastructure and growth kinetics were observed, the influencing factors of Cryptococcus biofilm formation were observed and analyzed, and the antifungal drug sensitivity of Cryptococcus neoformans biofilm in vitro was studied. [results] in vitro, the animal model showed that the mature Cryptococcus biofilm showed an organic three-dimensional structure and a typical microcolony / water channel configuration. The growth activity of Cryptococcus neoformans biofilm increased with the prolongation of culture time and stabilized gradually after reaching a certain maturity, and the ability of serum Cryptococcus type A to form biofilm was stronger than that of type B. The biofilm thickness and activity of Cryptococcus neoformans pretreated with cerebrospinal fluid and serum were increased, and the resistance of Cryptococcus neoformans to various antifungal drugs was increased. [conclusion] the existence of Cryptococcus biofilm was confirmed, the mature Cryptococcus biofilm showed an organic three-dimensional structure, and the growth activity of Cryptococcus biofilm increased obviously with the prolongation of culture time, and gradually stabilized after reaching a certain maturity. Different serotypes of Cryptococcus neoformans may have different ability to form biofilm, and cerebrospinal fluid and serum can promote the formation of biofilm of Cryptococcus neoformans. The sensitivity of Cryptococcus neoformans to various antifungal drugs was significantly decreased and the drug resistance was enhanced under the condition of biofilm.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R519;R379

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