A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata
A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata
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DOI：
10.1073/pnas.0611195104
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发表时间：
2007-05-01
影响因子：
11.1
通讯作者：
Cormack, Brendan P.
中科院分区：
文献类型：
--
作者：
Kaur, Rupinder;Ma, Biao;Cormack, Brendan P.
光滑念珠菌是人类的酵母病原体。我们建立了组织培养模型来分析光滑念珠菌与巨噬细胞的相互作用。巨噬细胞摄取的酵母的转录谱揭示了代谢的总体变化以及编码细胞外糖基磷脂酰肌醇连接的乙酰蛋白酶的基因家族（YPS基因）的表达增加。这些YPS基因中的八个被发现在一个集群中，这是唯一的光滑念珠菌。遗传分析表明，光滑念珠菌YPS基因是细胞壁完整性、粘附哺乳动物细胞、在巨噬细胞中存活和毒力所必需的。通过监测细胞壁粘附素Epa1的处理，我们还表明Yps蛋白酶通过去除和释放糖基磷脂酰肌醇锚定的细胞壁蛋白在细胞壁重塑中发挥重要作用。
Candida glabrata is a yeast pathogen of humans. We have established a tissue culture model to analyze the interaction of C glabrata with macrophages. Transcript profiling of yeast ingested by macrophages reveals global changes in metabolism as well as increased expression of a gene family (YPS genes) encoding extracellular glycosylphosphatidylinositol-linked aspartyl proteases. Eight of these YPS genes are found in a cluster that is unique to C glabrata. Genetic analysis shows that the C glabrata YPS genes are required for cell wall integrity, adherence to mammalian cells, survival in macrophages and virulence. By monitoring the processing of a cell wall adhesin, Epa1, we also show that Yps proteases play an important role in cell wall re-modeling by removal and release of glycosylphosphatidylinositol-anchored cell wall proteins.