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模式暗色丝孢菌皮炎外瓶霉的分子遗传学研究

Molecular genetic studies of the model dematiaceous pathogen Wangiella dermatitidis.

作者信息

Szaniszlo Paul J

机构信息

Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712-1095, USA.

出版信息

Int J Med Microbiol. 2002 Oct;292(5-6):381-90. doi: 10.1078/1438-4221-00221.

DOI:10.1078/1438-4221-00221
PMID:12452284
Abstract

The rapidly improving molecular genetic tractability of Wangiella (Exophiala) dermatitidis significantly enhances its usefulness as a model for the more than 100 other dematiaceous (melanized) agents of human disease. Previously this model was based almost exclusively on its vegetative polymorphism, which at the simplest level is expressed as three well-characterized modes of growth (e.g., blastic, apical and isotropic) that produce myriad yeast, hyphal and sclerotic phenotypes. This cellular plasticity is important for a dematiaceous model pathogen because some are hyphal in nature but exist almost exclusively as sclerotic bodies in infected tissue, whereas others are hyphal both in nature and in tissue, and still others exist in nature predominantly as yeast, but as mixtures of yeast, hyphae and sclerotic bodies in tissue. By exploiting the polymorphism of W. dermatitidis, any phenotype of another dematiaceous pathogen can be produced for study of the regulation of its development and its contribution to pathogenicity and virulence. The coupling of this asset with the recent finding that its haploid, uninucleate yeast cell is easily transformed molecularly, and the even more recent development of systems for both random and targeted gene disruptions and for site-specific, integrative gene overexpression studies suggest that it will continue as the preferred model for the dematiaceous fungi and irrespective of the mycosis involved. The results reviewed here aim to confirm this contention, stimulate others to study this fungus, and demonstrate that W. dermatitidis is exceptionally useful for discovering by molecular genetic techniques cell wall-associated virulence factors in fungi, and in particular in the dematiaceous fungi.

摘要

皮炎外瓶霉(Wangiella (Exophiala) dermatitidis)分子遗传学易处理性的迅速提高,显著增强了其作为人类疾病中100多种其他暗色(黑化)病原体模型的实用性。此前,该模型几乎完全基于其营养多态性,在最简单的层面上,这种多态性表现为三种特征明确的生长模式(例如,芽生、顶端生长和各向同性生长),这些生长模式产生了无数的酵母、菌丝和硬化体表型。这种细胞可塑性对于暗色模型病原体很重要,因为有些病原体本质上是菌丝,但在感染组织中几乎完全以硬化体形式存在,而另一些病原体在本质上和组织中都是菌丝,还有一些病原体在自然界中主要以酵母形式存在,但在组织中以酵母、菌丝和硬化体的混合物形式存在。通过利用皮炎外瓶霉的多态性,可以产生另一种暗色病原体的任何表型,用于研究其发育调控及其对致病性和毒力的贡献。这一特性与最近发现其单倍体、单核酵母细胞易于进行分子转化,以及最近开发的用于随机和靶向基因破坏以及用于位点特异性、整合基因过表达研究的系统相结合,表明它将继续作为暗色真菌的首选模型,而不论所涉及的真菌病如何。这里回顾的结果旨在证实这一观点,激励其他人研究这种真菌,并证明皮炎外瓶霉对于通过分子遗传学技术发现真菌尤其是暗色真菌中与细胞壁相关的毒力因子非常有用。

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