The Candida albicans cell wall protein Rhd3/Pga29 is abundant in the yeast form and contributes to virulence
The Candida albicans cell wall protein Rhd3/Pga29 is abundant in the yeast form and contributes to virulence
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DOI：
10.1002/yea.1790
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发表时间：
2010-08-01
期刊：
影响因子：
2.6
通讯作者：
Weig, Michael
中科院分区：
文献类型：
--
作者：
de Boer, Albert D.;de Groot, Piet W. J.;Weig, Michael
人类病原菌白色念珠菌的糖基化磷脂酰肌醇修饰蛋白Rhd3/Pga29属于细胞壁蛋白家族，在念珠菌中广泛存在，但在其他真菌中没有发现。PGa29通过β-1，6-葡聚糖共价连接到细胞壁的β-1，3-葡聚糖骨架上。它是一种小而丰富的O-糖基化蛋白，需要蛋白质-O-甘露糖基转移酶Pmt1进行糖基化。此外，PGa29在酵母细胞中强烈表达，但在菌丝中表达下调。在白色念珠菌中去除PGA29基因会导致细胞壁甘露聚糖的显著减少；然而，PGa29似乎在维持细胞壁完整性方面没有主要作用。此外，pga29缺失突变体的黏附能力和菌丝形成也是正常的。重要的是，pga29缺失突变体的毒力较小，pga29突变体感染重组人上皮后，导致促炎性细胞因子如GM-CSF、TNF、IL-6和IL-8的诱导减少。我们认为，pga29突变体的毒力降低是表面属性改变的结果，导致真菌识别改变。(C)版权所有2010 John Wiley&Sons，Ltd.
The glycosylphosphatidylinositol-modified protein Rhd3/Pga29 of the human pathogen Candida albicans belongs to a family of cell wall proteins that are widespread among Candida species but are not found in other fungi. Pga29 is covalently linked to the beta-1,3-glucan framework of the cell wall via beta-1,6-glucan. It is a small and abundant O-glycosylated protein and requires the protein-O-mannosyl transferase Pmt1 for glycosylation. Furthermore, Pga29 is strongly expressed in yeast cells but is downregulated in hyphae. Removal of the PGA29 gene in C. albicans leads to a significant reduction of cell wall mannan; however, Pga29 does not seem to have a major role in maintaining cell wall integrity. In addition, adhesion capacity and hyphae formation appear normal in pga29 deletion mutants. Importantly, the pga29 deletion mutant is less virulent, and infection of reconstituted human epithelium with the pga29 mutant results in a diminished induction of proinfiammatory cytokines, such as GM-CSF, TNF, IL-6 and IL-8. We propose that the reduced virulence of the pga29 mutant is a consequence of altered surface properties, resulting in altered fungal recognition. (C) Copyright 2010 John Wiley & Sons, Ltd.