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PNAS:隐球菌致病性研究

科技动态
来源: 标签:球菌致病性研究 2009-09-03 11:06:34
  科学家发现了他们认为是让一种新发真菌菌株进化并导致自1999年起温哥华岛的几例死亡的原因。这项发现可能有助于科学家理解为什么这种导致了全世界非常少的感染病例的真菌在西北太平洋地区变得致命。

  科学家发现了他们认为是让一种新发真菌菌株进化并导致自1999年起温哥华岛的几例死亡的原因。这项发现可能有助于科学家理解为什么这种导致了全世界非常少的感染病例的真菌在西北太平洋地区变得致命。

  Robin May及其同事发现,隐球菌(Cryptococcus gattii)温哥华岛暴发菌株显著增加了其在一种称为巨噬细胞的免疫细胞内部的繁殖能力。巨噬细胞通常帮助抵御寄生虫。这种真菌在巨噬细胞内部的繁殖削弱了宿主抵御感染和启动合适的免疫应答的能力,这解释了为什么健康人在这场暴发中死亡或者生病。尽管许多病原体试图在细胞内躲避免疫系统,并利用宿主细胞的能源供应和原材料,这组作者发现了温哥华岛暴发菌株上调了一大组基因的表达,这些基因或者在该菌株的制造能量的线粒体内部,或者与其有关。线粒体改变了状态,这有助于这种真菌在巨噬细菌的消化细胞器内部的破坏性环境中生存。这组作者说,线粒体产生的这种变化可能是其他病原体采用的一种策略。(生物谷Bioon.com)

  生物谷推荐原始出处:

  PNAS doi: 10.1073/pnas.0902963106

  The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation

  Hansong Maa, Ferry Hagenb,c, Dov J. Stekela, Simon A. Johnstona, Edward Sionovd, Rama Falkd, Itzhack Polacheckd, Teun Boekhoutb,c and Robin C. Maya,1

  In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we show that the Vancouver Island outbreak (VIO) isolates have dramatically increased their ability to replicate within macrophages of the mammalian immune system in comparison with other C. gattii strains. We further demonstrate that such enhanced intracellular parasitism is directly linked to virulence in a murine model of cryptococcosis, suggesting that this phenotype may be the cause of the outbreak. Finally, microarray studies on 24 C. gattii strains reveals that the hypervirulence of the VIO isolates is characterized by the up-regulation of a large group of genes, many of which are encoded by mitochondrial genome or associated with mitochondrial activities. This expression profile correlates with an unusual mitochondrial morphology exhibited by the VIO strains after phagocytosis. Our data thus demonstrate that the intracellular parasitism of macrophages is a key driver of a human disease outbreak, a finding that has significant implications for a wide range of other human pathogens.

 

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