Global analysis of fungal morphology exposes mechanisms of host cell escape.
Global analysis of fungal morphology exposes mechanisms of host cell escape.
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DOI：
10.1038/ncomms7741
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发表时间：
2015-03-31
影响因子：
16.6
通讯作者：
Cowen, Leah E.
中科院分区：
文献类型：
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作者：
O'Meara, Teresa R.;Veri, Amanda O.;Ketela, Troy;Jiang, Bo;Roemer, Terry;Cowen, Leah E.
单细胞酵母和多细胞丝之间的发育转变支撑着多种真菌病原体的毒力。对于主要的人类真菌病原体白色念珠菌来说，丝状化被认为是免疫细胞通过诱导炎症性程序性细胞死亡而逃逸所必需的。在这里，我们对白色念珠菌形态发生进行了基因组规模的分析，并鉴定了 102 个负形态发生调节因子和 872 个正调节因子，强调了麦角甾醇生物合成和 N 连接糖基化的关键作用。我们证明白色念珠菌丝状化并不是逃离宿主免疫细胞所必需的；相反，巨噬细胞焦亡是由真菌细胞壁重塑和糖基化蛋白响应巨噬细胞吞噬体的暴露驱动的。在远亲真菌病原体新型隐球菌中也观察到了杀死的、先前被吞噬的细胞驱动巨噬细胞裂解的能力。这项研究提供了控制关键毒力特征的形态发生回路的全局视图，并阐明了真菌触发宿主细胞死亡的新机制。 几种病原真菌（例如白色念珠菌）经历单细胞形式和多细胞丝状体之间的转变。在这里，作者对白色念珠菌进行了基因组规模的分析，结果表明，与普遍看法相反，丝状化并不是逃离宿主免疫细胞所必需的。
Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. Several pathogenic fungi such as Candida albicans undergo transitions between single-celled forms and multicellular filaments. Here the authors perform a genome-scale analysis of C. albicans and show that, contrary to common belief, filamentation is not required for escape from host immune cells.
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影响因子：
56.9
作者：
Ryan, Owen;Shapiro, Rebecca S.;Boone, Charles
通讯作者：
Boone, Charles
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Onyewu, C;Blankenship, JR;Heitman, J
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Lo, HJ;Kohler, JR;Fink, GR
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Smith AM;Heisler LE;St Onge RP;Farias-Hesson E;Wallace IM;Bodeau J;Harris AN;Perry KM;Giaever G;Pourmand N;Nislow C
通讯作者：
Nislow C
影响因子：
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