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Interactions between human phagocytes and Candida albicans biofilms alone and in combination with antifungal agents.
抗真菌药物对于人类吞噬细胞与白色念珠菌被膜关系的影响

出处: J Infect Dis   2010   Jun   201 (12) :1941-9

作者:Katragkou A;Kruhlak MJ;Simitsopoulou M;Chatzimoschou A;Taparkou A;Cotten CJ;Paliogianni F;Diza-Mataftsi E;Tsantali C;Walsh TJ;Roilides E

PMID:20415537

BACKGROUND: Biofilm formation is an important component of vascular catheter infections caused by Candida albicans. Little is known about the interactions between human phagocytes, antifungal agents, and Candida biofilms. METHODS: The interactions between C. albicans biofilms and human phagocytes alone and in combination with anidulafungin or voriconazole were investigated and compared with their corresponding planktonic counterparts by means of an in vitro biofilm model with clinical intravascular and green fluorescent protein (GFP)-expressing strains. Phagocyte-mediated and antifungal agent-mediated damages were determined by 2,3-bis[ 2- methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide assay, and structural effects were visualized by confocal microscopy. Oxidative burst was evaluated by flow cytometric measurement of dihydrorhodamine 123 oxidation, and cytokine release was measured by enzyme-linked immunosorbent assay. RESULTS: Phagocytes alone and in combination with antifungal agents induced less damage against biofilms compared with planktonic cells. However, additive effects occurred between phagocytes and anidulafungin against Candida biofilms. Confocal microscopy demonstrated the absence of phagocytosis within biofilms but marked destruction caused by anidulafungin and phagocytes. Anidulafungin but not voriconazole elicited tumor necrosis factor alpha release from phagocytes compared with that from untreated biofilms. CONCLUSIONS: C. albicans within biofilms are more resistant to phagocytic host defenses but are susceptible to additive effects between phagocytes and an echinocandin.

背景:生物被膜的形成是白色念珠菌性血管内导管相关感染的重要组成部分。目前,对于人吞噬细胞、白色念珠菌生物被膜、抗真菌药物之间的关系知之甚少。<br>方法:采用分离自临床血管内和表达绿色荧光蛋白(GFP)菌株的体外生物被膜模型,比较吞噬细胞在与阿尼芬净或伏立康唑联合或单独存在状态下与白色念珠菌被膜的关系,并与其浮游状态进行比较。以2,3-二[ 2-甲氧基-4-硝基-5-磺苯基]2H-四唑-5-甲酰苯胺法检测吞噬细胞和抗真菌药物介导的杀伤作用,其结构效应由共聚焦显微镜显影。以流式细胞术测定二氢罗丹明123的氧化来反映氧爆发,酶联免疫吸附试验检测细胞因子释放。<br>结果:吞噬细胞在抗真菌药联合或单独存在状态对于生物被膜的破坏程度弱于漂浮细胞。然而,吞噬细胞和阿尼芬净对于破坏念珠菌性生物被膜具有相加效应。共聚焦显微镜显示,生物被膜中不存在吞噬细胞,而吞噬细胞和阿尼芬净可显著破坏生物被膜的结构。较之于未处理的生物被膜,阿尼芬净可以促使吞噬细胞释放TNFα,而伏立康唑没有这种作用。<br>结论:存在于生物被膜中的白色念珠菌对于宿主吞噬细胞防御作用具有更强的抵抗力,但是对于吞噬细胞和棘白菌素的附加效应敏感。