In vivo inhibitory effect on the biofilm formation of Candida albicans by liverwort derived riccardin D.
In vivo inhibitory effect on the biofilm formation of Candida albicans by liverwort derived riccardin D.
复制标题
地衣衍生的 Riccardin D 对白色念珠菌生物膜形成的体内抑制作用。
DOI：
10.1371/journal.pone.0035543
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lou H
中科院分区：
文献类型：
--
作者：
Li Y;Ma Y;Zhang L;Guo F;Ren L;Yang R;Li Y;Lou H
Riccardin D 是从中国地钱 Dumortiera hirsute 中分离出来的大环双联苯甲基，体外研究证明对白色念珠菌生物膜形成具有抑制作用。我们目前的研究旨在探讨 riccardin D 单独使用或与临床使用抗真菌药物氟康唑联合使用时对白色念珠菌生物膜的体内作用和机制。 XTT还原试验显示，在使用中心静脉导管相关的感染动物模型时，riccardin D对白色念珠菌生物膜形成具有剂量依赖性的预防和治疗作用。扫描电镜和激光共聚焦扫描显微镜显示，Ricardin D处理后生物膜形态发生显着改变，尤其是菌丝生长受到抑制。为了揭示潜在的分子机制，进行定量实时RT-PCR来观察相关基因的变化。 riccardin D处理后菌丝特异性基因如ALS1、ALS3、ECE1、EFG1、HWP1和CDC35的下调表明riccardin D抑制Ras-cAMP-Efg通路从而延缓菌丝形成，从而导致生物膜成熟缺陷。此外，当与氟康唑联合给药时，riccardin D 显示出增强的抗真菌活性。我们的研究为消除相关病原体的生物膜提供了潜在的临床应用。
Riccardin D, a macrocyclic bisbibenzyl isolated from Chinese liverwort Dumortiera hirsute, has been proved to have inhibitory effect on biofilms formation of Candida albicans in in vitro study. Our present study aims to investigate the in vivo effect and mechanisms of riccardin D against C. albicans biofilms when used alone or in combination with clinical using antifungal agent fluconazole. XTT reduction assay revealed riccardin D had both prophylactic and therapeutic effect against C. albicans biofilms formation in a dose-dependent manner when using a central venous catheter related infective animal model. Scanning electron microscope and laser confocal scanning microscope showed that the morphology of biofilms was altered remarkably after riccardin D treatment, especially hypha growth inhibition. To uncover the underlying molecular mechanisms, quantitative real-time RT-PCR was performed to observe the variation of related genes. The downregulation of hypha-specific genes such as ALS1, ALS3, ECE1, EFG1, HWP1 and CDC35 following riccardin D treatment suggested riccardin D inhibited the Ras-cAMP-Efg pathway to retard the hypha formation, then leading to the defect of biofilms maturation. Moreover, riccardin D displayed an increased antifungal activity when administered in combination with fluconazole. Our study provides a potential clinical application to eliminate the biofilms of relevant pathogens.
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影响因子：
3.7
作者：
Iwai Y;Murakami K;Gomi Y;Hashimoto T;Asakawa Y;Okuno Y;Ishikawa T;Hatakeyama D;Echigo N;Kuzuhara T
通讯作者：
Kuzuhara T
影响因子：
5.9
作者：
Anaissie, EJ;Rex, JH;Vartivarian, S
通讯作者：
Vartivarian, S
影响因子：
3.6
作者：
Leberer, E;Harcus, D;Schröppel, K
通讯作者：
Schröppel, K
影响因子：
11.8
作者：
Edmond, MB;Wallace, SE;Wenzel, RP
通讯作者：
Wenzel, RP
影响因子：
3.1
作者：
Andes, D;Nett, J;Pitula, A
通讯作者：
Pitula, A