In vitro and in vivo effects of suloctidil on growth and biofilm formation of the opportunistic fungus Candida albicans.
In vitro and in vivo effects of suloctidil on growth and biofilm formation of the opportunistic fungus Candida albicans.
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舒洛地尔对机会性真菌白色念珠菌生长和生物膜形成的体外和体内影响
DOI：
10.18632/oncotarget.19542
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发表时间：
2017-09-19
期刊：
影响因子：
--
通讯作者：
Zhou Y
中科院分区：
文献类型：
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作者：
Zeng B;Li J;Wang Y;Chen P;Wang X;Cui J;Liu L;Hu X;Cao Q;Xiao Y;Dong J;Sun Y;Zhou Y
作为人类最常见的真菌病原体，白色念珠菌可产生严重的耐药性，因为其生物膜对大多数抗真菌药物具有耐药性;这导致迫切需要开发新的抗真菌药物。在这里，我们评估了抗血栓药物舒洛地尔对C。白念珠菌生物膜的体外和体内研究。我们发现舒洛地尔对C.白色念珠菌生物膜，最低抑制浓度（MIC 80）为4 μg/mL，生物膜抑制浓度（BIC 80）为16 μg/mL，生物膜根除浓度（BEC 80）为64 μg/mL。时间-杀灭曲线显示舒洛地尔具有浓度依赖性。扫描电子显微镜图像清楚地显示了舒洛地尔对生物膜的形态学影响。酵母-菌丝型转换是C.因此，我们进行了菌丝生长试验，并观察到舒洛地尔抑制酵母菌到菌丝的形态转换。该结果与舒洛地尔处理后菌丝特异性基因（HWP 1、ALS 3和ECE 1）表达水平的下调一致。体内实验中，256 μg/mL舒洛地尔治疗组真菌计数较未治疗组显著降低（P<0.01），治疗组组织学反应轻微，尤其是治疗5 d后（P<0.01）。总而言之，我们的数据表明舒洛地尔是一种潜在的抗真菌剂。
As the most frequent fungal pathogen in humans, Candida albicans can develop serious drug resistance because its biofilms are resistant to most antifungal agents; this leads to an urgent need to develop novel antifungals. Here, we evaluated the efficacy of an antithrombotic drug, suloctidil, against C. albicans biofilms in vitro and in vivo. We found that suloctidil is effective to inhibit C. albicans biofilm, with a minimum inhibitory concentration (MIC80) of 4 μg/mL, a biofilm inhibiting concentration (BIC80) of 16 μg/mL and a biofilm eradicating concentration (BEC80) of 64 μg/mL. Furthermore, the concentration-dependent characteristics of suloctidil were shown by its time-kill curves. Scanning electron microscopy images clearly revealed the morphological effects of suloctidil on biofilm. Yeast-to-hyphal form switching is a key virulence factor of C. albicans; therefore, we performed hyphal growth tests and observed that suloctidil inhibited yeast-to-hyphal form switching. This result was consistent with the down-regulation of hypha-specific gene (HWP1, ALS3, and ECE1) expression levels after suloctidil treatment. In vivo, 256 μg/mL of suloctidil significantly reduced fungal counts (P<0.01) compared to that in groups without treatment; the treatment group induced a slight histological reaction, especially when the treatment lasted for 5 days (P<0.01). Taken together, our data suggest that suloctidil is a potential antifungal agent.