Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA.
Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.
Sci Rep. 2017 Jun 6;7(1):2908. doi: 10.1038/s41598-017-03082-4.
Candida albicans is an opportunistic fungal pathogen colonizing the oral cavity. C. albicans secreted aspartic protease Sap6 is important for virulence during oral candidiasis since it degrades host tissues to release nutrients and essential transition metals. We found that zinc specifically increased C. albicans autoaggregation induced by Sap6; and that Sap6 itself bound zinc ions. In silico analysis of Sap6 predicted four amyloidogenic regions that were synthesized as peptides (P1-P4). All peptides, as well as full length Sap6, demonstrated amyloid properties, and addition of zinc further increased amyloid formation. Disruption of amyloid regions by Congo red significantly reduced auotoaggregation. Deletion of C. albicans genes that control zinc acquisition in the ZAP1 regulon, including zinc transporters (Pra1 and Zrt1) and other zinc-regulated surface proteins, resulted in lower autoaggregation and reduction of surface binding of Sap6. Cells with high expression of PRA1 and ZRT1 also showed increased Sap6-mediated autoaggregation. C. albicans ∆sap6 deletion mutants failed to accumulate intracellular zinc comparable to ∆zap1, ∆zrt1, and ∆pra1 cells. Thus Sap6 is a multi-functional molecule containing amyloid regions that promotes autoaggregation and zinc uptake, and may serve as an additional system for the community acquisition of zinc.
白色念珠菌是一种定植于口腔的机会性真菌病原体。白色念珠菌分泌的天冬氨酸蛋白酶 Sap6 对口腔念珠菌病的毒力很重要，因为它降解宿主组织以释放营养物质和必需的过渡金属。我们发现锌特异性增加了 Sap6 诱导的白色念珠菌自聚集；并且 Sap6 本身结合锌离子。Sap6 的计算机分析预测了四个淀粉样蛋白形成区域，这些区域被合成肽（P1-P4）。所有肽以及全长 Sap6 都表现出淀粉样特性，并且添加锌进一步增加了淀粉样形成。刚果红对淀粉样区域的破坏显著降低了自聚集。敲除控制 ZAP1 调控子中锌摄取的白色念珠菌基因，包括锌转运蛋白（Pra1 和 Zrt1）和其他锌调节表面蛋白，导致自聚集降低，Sap6 表面结合减少。高表达 PRA1 和 ZRT1 的细胞也显示出 Sap6 介导的自聚集增加。白色念珠菌∆sap6 缺失突变体不能积累与∆zap1、∆zrt1 和∆pra1 细胞相当的细胞内锌。因此，Sap6 是一种包含促进自聚集和锌摄取的淀粉样区域的多功能分子，并且可以作为社区获取锌的附加系统。
