Department of Medical Microbiology and National Reference Centre for Systemic Mycoses, University Medical Centre Göttingen, Kreuzbergring 57, D-37075 Germany.
Yeast. 2010 Aug;27(8):611-24. doi: 10.1002/yea.1790.
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 proinflammatory 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.
人源病原体白色念珠菌的糖基磷脂酰肌醇修饰蛋白 Rhd3/Pga29 属于一种广泛存在于念珠菌属但不存在于其他真菌中的细胞壁蛋白家族。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-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，但在菌丝中下调。在白色念珠菌中去除 PGA29 基因会导致细胞壁甘露聚糖显著减少；然而，Pga29 在维持细胞壁完整性方面似乎没有主要作用。此外，在 pga29 缺失突变体中，粘附能力和菌丝形成似乎正常。重要的是，pga29 缺失突变体的毒力降低，用 pga29 突变体感染重建的人上皮细胞会导致促炎细胞因子（如 GM-CSF、TNF、IL-6 和 IL-8）的诱导减少。我们提出，pga29 突变体的毒力降低是由于表面特性的改变，导致真菌识别的改变。
