Kronstad Jim, Saikia Sanjay, Nielson Erik David, Kretschmer Matthias, Jung Wonhee, Hu Guanggan, Geddes Jennifer M H, Griffiths Emma J, Choi Jaehyuk, Cadieux Brigitte, Caza Mélissa, Attarian Rodgoun
The Michael Smith Laboratories, Department of Microbiology and Immunology, and Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC, Canada.
Eukaryot Cell. 2012 Feb;11(2):109-18. doi: 10.1128/EC.05273-11. Epub 2011 Dec 2.
The basidiomycete fungus Cryptococcus neoformans infects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system. Recent studies provide insights into mechanisms of adaptation during this transition that include the expression of antiphagocytic functions, the remodeling of central carbon metabolism, the expression of specific nutrient acquisition systems, and the response to hypoxia. Specific transcription factors regulate these functions as well as the expression of one or more of the major known virulence factors of C. neoformans. Therefore, virulence factor expression is to a large extent embedded in the regulation of a variety of functions needed for growth in mammalian hosts. In this regard, the complex integration of these processes is reminiscent of the master regulators of virulence in bacterial pathogens.
担子菌纲真菌新型隐球菌通过吸入来自环境的干燥酵母细胞或孢子感染人类。在缺乏有效的免疫控制时，初始肺部感染常常扩散至中枢神经系统，导致脑膜脑炎。因此，该真菌必须从环境过渡到不同的哺乳动物生态位，这些生态位包括吞噬细胞的细胞内区域以及肺、血液和中枢神经系统中的细胞外部位。最近的研究为这一过渡过程中的适应机制提供了见解，这些机制包括抗吞噬功能的表达、中心碳代谢的重塑、特定营养获取系统的表达以及对缺氧的反应。特定转录因子调节这些功能以及新型隐球菌一种或多种主要已知毒力因子的表达。因此，毒力因子的表达在很大程度上嵌入在对哺乳动物宿主生长所需的多种功能的调节中。在这方面，这些过程的复杂整合让人联想到细菌病原体中毒力的主要调节因子。
