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舒洛地尔对该机会性真菌生长和生物膜形成的影响。

and effects of suloctidil on growth and biofilm formation of the opportunistic fungus .

作者信息

Zeng Beini, Li Jiachen, Wang Yajie, Chen Pengxiang, Wang Xiaohong, Cui Jianfeng, Liu Lidong, Hu Xiaoyan, Cao Qian, Xiao Ying, Dong Junlu, Sun Yundong, Zhou Yabin

机构信息

Department of Pathogenic Biology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, People's Republic of China.

Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People's Republic of China.

出版信息

Oncotarget. 2017 Jul 25;8(41):69972-69982. doi: 10.18632/oncotarget.19542. eCollection 2017 Sep 19.

Abstract

As the most frequent fungal pathogen in humans, 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 biofilms and . We found that suloctidil is effective to inhibit biofilm, with a minimum inhibitory concentration (MIC) of 4 μg/mL, a biofilm inhibiting concentration (BIC) of 16 μg/mL and a biofilm eradicating concentration (BEC) 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 ; 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 (, and ) expression levels after suloctidil treatment. , 256 μg/mL of suloctidil significantly reduced fungal counts (<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 (<0.01). Taken together, our data suggest that suloctidil is a potential antifungal agent.

摘要

作为人类中最常见的真菌病原体,由于其生物膜对大多数抗真菌剂具有抗性,因此会产生严重的耐药性;这导致迫切需要开发新型抗真菌药物。在此,我们评估了抗血栓药物舒洛地尔对生物膜和的疗效。我们发现舒洛地尔对抑制生物膜有效,其最低抑菌浓度(MIC)为4μg/mL,生物膜抑制浓度(BIC)为16μg/mL,生物膜根除浓度(BEC)为64μg/mL。此外,舒洛地尔的时间杀菌曲线显示出其浓度依赖性特征。扫描电子显微镜图像清楚地揭示了舒洛地尔对生物膜的形态学影响。酵母到菌丝形态的转变是的一个关键毒力因子;因此,我们进行了菌丝生长试验,观察到舒洛地尔抑制了酵母到菌丝形态的转变。该结果与舒洛地尔处理后菌丝特异性基因(,和)表达水平的下调一致。,与未处理组相比,256μg/mL的舒洛地尔显著降低了真菌数量(<0.01);治疗组引起了轻微的组织学反应,尤其是治疗持续5天时(<0.01)。综上所述,我们的数据表明舒洛地尔是一种潜在的抗真菌剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6776/5642531/2a829b11dd20/oncotarget-08-69972-g001.jpg

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