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塑造真菌适应组——烟曲霉的应激反应。

Shaping the fungal adaptome--stress responses of Aspergillus fumigatus.

机构信息

Research Center for Infectious Diseases, Julius-Maximilians-University Würzburg, Germany.

出版信息

Int J Med Microbiol. 2011 Jun;301(5):408-16. doi: 10.1016/j.ijmm.2011.04.008. Epub 2011 May 11.

Abstract

Aspergillus fumigatus as prime pathogen to cause aspergillosis has evolved as a saprophyte, but is also able to infect and colonise immunocompromised hosts. Based on the 'dual use' hypothesis of fungal pathogenicity, general characteristics have to be considered as unspecific virulence determinants, among them stress adaptation capacities. The susceptible, warm-blooded mammalian host represents a specific ecological niche that poses several kinds of stress conditions to the fungus during the course of infection. Detailed knowledge about the cellular pathways and adaptive traits that have evolved in A. fumigatus to counteract situations of stress and varying environmental conditions is crucial for the identification of novel and specific antifungal targets. Comprehensive profiling data accompanied by mutant analyses have shed light on such stressors, and nutritional deprivation, oxidative stress, hypoxia, elevated temperature, alkaline pH, extensive secretion, and, in particular during treatment with antifungals, cell membrane perturbations appear to represent the major hazards A. fumigatus has to cope with during infection. Further efforts employing innovative approaches and advanced technologies will have to be made to expand our knowledge about the scope of the A. fumigatus adaptome that is relevant for disease.

摘要

烟曲霉作为引起曲霉菌病的主要病原体,已经进化为一种腐生物,但也能够感染和定植免疫功能低下的宿主。基于真菌致病性的“两用”假说,一般特征被认为是非特异性毒力决定因素,其中包括应激适应能力。易感的、温血的哺乳动物宿主代表了一种特定的生态位,在感染过程中,真菌会面临多种应激条件。详细了解烟曲霉在应对应激和环境条件变化时进化出的细胞途径和适应性特征,对于确定新型和特异性抗真菌靶标至关重要。全面的分析数据和突变体分析揭示了这些应激因素,包括营养剥夺、氧化应激、缺氧、高温、碱性 pH 值、大量分泌,特别是在使用抗真菌药物治疗期间,细胞膜扰动似乎是烟曲霉在感染过程中必须应对的主要危害。需要进一步努力采用创新方法和先进技术,以扩大我们对与疾病相关的烟曲霉适应组范围的了解。

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