High-content phenotypic screenings to identify inhibitors of Candida albicans biofilm formation and filamentation.
High-content phenotypic screenings to identify inhibitors of Candida albicans biofilm formation and filamentation.
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DOI：
10.1111/2049-632x.12161
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发表时间：
2014-04
影响因子：
3.3
通讯作者：
Lopez-Ribot JL
中科院分区：
文献类型：
--
作者：
Pierce CG;Saville SP;Lopez-Ribot JL
念珠菌属是世界范围内机会性真菌感染的主要原因，白色念珠菌仍然是念珠菌病最常见的病原体，目前是第三至第四大最常见的医院感染。这些感染通常与高发病率和死亡率相关，主要是由于目前抗真菌药物的疗效有限。In C.白色念珠菌在酵母和丝状形式之间的形态发生转化和生物膜形成代表了与该真菌的生物学密切相关的两个重要生物学过程，并且在念珠菌病的发病机制中也起重要作用。我们使用来自国家癌症研究所开放化学库的三种不同的化学文库进行了基于细胞的表型筛选，并鉴定了几种具有抗C.白色念珠菌生物膜形成和/或粘附。这些基于表型的方法代表了传统遗传学和基因组学技术的一个繁荣的替代方案，以解决实验上具有挑战性和复杂的生物学现象，如生物膜形成和抑制，同时为开发新的抗真菌药物开辟了新的可能性。
Candida species represent the main cause of opportunistic fungal infections worldwide, and Candida albicans remains the most common etiological agent of candidiasis, now the third to fourth most common nosocomial infection. These infections are typically associated with high morbidity and mortality, mainly due to the limited efficacy of current antifungal drugs. In C. albicans morphogenetic conversions between yeast and filamentous forms and biofilm formation represent two important biological processes that are intimately associated with the biology of this fungus, and also play important roles during the pathogenesis of candidiasis. We have performed cell-based phenotypic screens using three different chemical libraries from the National Cancer Institute’s Open Chemical Repository collection, and identified several compounds with inhibitory activity against C. albicans biofilm formation and/or filamentation. These phenotype-based approaches represent a prosperous alternative to conventional genetics and genomics techniques to address experimentally challenging and complex biological phenomena, such as biofilm formation and filamentation, while at the same time opening new possibilities for the development of new antifungal agents.