Tournu H, Serneels J, Van Dijck P
Flanders Interuniversity Institute for Biotechnology, Department of Molecular Microbiology, Katholieke Universiteit Leuven, Heverlee, Belgium.
Curr Drug Targets. 2005 Dec;6(8):909-22. doi: 10.2174/138945005774912690.
With the rise of fungal infection incidence amongst the patient population, the importance of developing new antifungal drug targets is higher than ever. This review mainly focuses on the three most prevalent fungal pathogens, Candida, Aspergillus and Cryptococcus, and on the most recent progresses in molecular research that contribute to a better understanding of the pathogen itself, but also its host and the interaction with its host. We consider the progress made in comparative genomics following the huge effort of fungal genome sequence projects undertaken in the last few years. We focus not only on currently used mammalian animal models such as mice, but also on novel non-mammalian models, such as the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, which offer useful tools in the area of the innate immune response to fungal infections. In addition we relate to the recent genomic and proteomic studies and focus on the use of these approaches in in vivo experiments in the pathogen itself as well as in the host. Finally, we describe the latest targeted mutagenesis strategy available in C. albicans and the use of RNA interference in both Cryptococcus neoformans and A. fumigatus. Our aim is not to give an exhaustive list of all new strategies but rather to give an overview of what will contribute most to the identification of new antifungal drug targets and the establishment of novel antifungal strategies.
随着患者群体中真菌感染发病率的上升，开发新的抗真菌药物靶点的重要性比以往任何时候都更高。本综述主要关注三种最常见的真菌病原体，即念珠菌、曲霉菌和隐球菌，以及分子研究的最新进展，这些进展有助于更好地了解病原体本身，以及它的宿主和与宿主的相互作用。我们考虑了过去几年真菌基因组测序项目付出巨大努力后在比较基因组学方面取得的进展。我们不仅关注目前使用的哺乳动物动物模型，如小鼠，还关注新型非哺乳动物模型，如线虫秀丽隐杆线虫和果蝇黑腹果蝇，它们在真菌感染的固有免疫反应领域提供了有用的工具。此外，我们涉及最近的基因组和蛋白质组学研究，并关注这些方法在病原体本身以及宿主的体内实验中的应用。最后，我们描述了白色念珠菌中可用的最新靶向诱变策略以及在新型隐球菌和烟曲霉中RNA干扰的应用。我们的目的不是详尽列举所有新策略，而是概述哪些将最有助于确定新的抗真菌药物靶点和建立新的抗真菌策略。
