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人类疾病中的真菌热休克蛋白

Fungal heat-shock proteins in human disease.

作者信息

Burnie James P, Carter Tracey L, Hodgetts Samantha J, Matthews Ruth C

机构信息

Department of Medical Microbiology, Clinical Sciences Building, University of Manchester, Manchester Royal Infirmary, Manchester, UK.

出版信息

FEMS Microbiol Rev. 2006 Jan;30(1):53-88. doi: 10.1111/j.1574-6976.2005.00001.x.

DOI:10.1111/j.1574-6976.2005.00001.x
PMID:16438680
Abstract

Heat-shock proteins (hsps) have been identified as molecular chaperones conserved between microbes and man and grouped by their molecular mass and high degree of amino acid homology. This article reviews the major hsps of Saccharomyces cerevisiae, their interactions with trehalose, the effect of fermentation and the role of the heat-shock factor. Information derived from this model, as well as from Neurospora crassa and Achlya ambisexualis, helps in understanding the importance of hsps in the pathogenic fungi, Candida albicans, Cryptococcus neoformans, Aspergillus spp., Histoplasma capsulatum, Paracoccidioides brasiliensis, Trichophyton rubrum, Phycomyces blakesleeanus, Fusarium oxysporum, Coccidioides immitis and Pneumocystis jiroveci. This has been matched with proteomic and genomic information examining hsp expression in response to noxious stimuli. Fungal hsp90 has been identified as a target for immunotherapy by a genetically recombinant antibody. The concept of combining this antibody fragment with an antifungal drug for treating life-threatening fungal infection and the potential interactions with human and microbial hsp90 and nitric oxide is discussed.

摘要

热休克蛋白(hsps)已被鉴定为微生物和人类之间保守的分子伴侣,并根据其分子量和高度的氨基酸同源性进行分类。本文综述了酿酒酵母的主要热休克蛋白、它们与海藻糖的相互作用、发酵的影响以及热休克因子的作用。从该模型以及粗糙脉孢菌和两性绵霉获得的信息,有助于理解热休克蛋白在致病性真菌中的重要性,这些真菌包括白色念珠菌、新型隐球菌、曲霉属、荚膜组织胞浆菌、巴西副球孢子菌、红色毛癣菌、布氏根霉、尖孢镰刀菌、粗球孢子菌和耶氏肺孢子菌。这与蛋白质组学和基因组学信息相匹配,这些信息研究了热休克蛋白在响应有害刺激时的表达。真菌热休克蛋白90已被一种基因重组抗体鉴定为免疫治疗的靶点。本文讨论了将这种抗体片段与抗真菌药物结合用于治疗危及生命的真菌感染的概念,以及与人类和微生物热休克蛋白90和一氧化氮的潜在相互作用。

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