Turning on virulence: Mechanisms that underpin the morphologic transition and pathogenicity of Blastomyces.
Turning on virulence: Mechanisms that underpin the morphologic transition and pathogenicity of Blastomyces.
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DOI：
10.1080/21505594.2018.1449506
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发表时间：
2019-12
期刊：
影响因子：
5.2
通讯作者：
Klein BS
中科院分区：
文献类型：
--
作者：
McBride JA;Gauthier GM;Klein BS
这篇综述文章的重点是芽生菌病，皮肤芽生菌，吉尔克里斯蒂芽生菌，和寄生芽生菌的病原体的温度适应和毒力的机制。作为对温度的反应，芽生菌在菌丝和酵母之间进行可逆的形态转换，称为相变。对于芽生菌和相关的热二型真菌而言，向酵母的转化对于毒力是必不可少的。在酵母阶段，芽生菌上调基本毒力因子BAD 1，其促进与宿主细胞的附着，损害免疫细胞的活化，并减弱细胞因子的释放。芽生酵母还分泌二肽基肽酶IVA（DPPIVA），其是一种丝氨酸蛋白酶，其减弱从宿主免疫细胞释放的细胞因子的作用。芽生菌酵母的体内转录谱分析发现了参与锌清除的基因（例如PRA 1和ZRT 1），这些基因在小鼠肺部感染期间有助于毒力。对毒力重要的基因的发现和表征导致了关于新诊断、疫苗开发和药物发现的新靶点的床边进展。
This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, Blastomyces dermatitidis, Blastomyces gilchristii, and Blastomyces percursus. In response to temperature, Blastomyces undergoes a reversible morphologic switch between hyphae and yeast known as the phase transition. The conversion to yeast for Blastomyces and related thermally dimorphic fungi is essential for virulence. In the yeast phase, Blastomyces upregulates the essential virulence factor, BAD1, which promotes attachment to host cells, impairs activation of immune cells, and blunts cytokine release. Blastomyces yeast also secrete dipeptidyl-peptidase IVA (DPPIVA), a serine protease that blunts the action of cytokines released from host immune cells. In vivo transcriptional profiling of Blastomyces yeast has uncovered genes such as PRA1 and ZRT1 involved in zinc scavenging that contribute to virulence during murine pulmonary infection. The discovery and characterization of genes important for virulence has led to advances at the bedside regarding novel diagnostics, vaccine development, and new targets for drug discovery.
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影响因子：
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