The pathogenic yeast Candida glabrata is reliant on a suite of cell surface adhesins that play a variety of roles necessary for transmission, establishment and proliferation during infection. One particular adhesin, Epithelial Adhesin 1 [Epa1p], is responsible for binding to host tissue, a process which is essential for fungal propagation. Epa1p structure consists of three domains: an N-terminal intercellular binding domain responsible for epithelial cell binding, a C-terminal GPI anchor for cell wall linkage and a serine/threonine-rich linker domain connecting these terminal domains. The linker domain contains a 40-amino acid tandem repeat region, which we have found to be variable in repeat copy number between isolates from clinical sources. We hypothesized that natural variation in Epa1p repeat copy may modulate protein function. To test this, we recombinantly expressed Epa1p with various repeat copy numbers in S. cerevisiae to determine how differences in repeat copy number affect Epa1p expression, surface display and binding to human epithelial cells. Our data suggest that repeat copy number variation has pleiotropic effects, influencing gene expression, protein surface display and shedding from the cell surface of the Epa1p adhesin. This study serves to demonstrate repeat copy number variation can modulate protein function through a number of mechanisms in order to contribute to pathogenicity of C. glabrata.

中文翻译：

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上皮粘附素 1 串联重复区域通过多种机制介导蛋白质展示。

致病性光滑念珠菌依赖于一系列细胞表面粘附素，这些粘附素在感染过程中发挥传播、建立和增殖所需的多种作用。一种特殊的粘附素，上皮粘附素 1 [Epa1p]，负责与宿主组织结合，这是真菌繁殖所必需的过程。Epa1p结构由三个结构域组成：负责上皮细胞结合的N端细胞间结合结构域、用于细胞壁连接的C端GPI锚以及连接这些末端结构域的富含丝氨酸/苏氨酸的接头结构域。连接结构域包含一个 40 个氨基酸的串联重复区域，我们发现临床来源的分离株之间的重复拷贝数存在差异。我们假设 Epa1p 重复拷贝的自然变异可能调节蛋白质功能。为了测试这一点，我们在酿酒酵母中重组表达了具有不同重复拷贝数的 Epa1p，以确定重复拷贝数的差异如何影响 Epa1p 表达、表面展示以及与人上皮细胞的结合。我们的数据表明，重复拷贝数变异具有多效性，影响基因表达、蛋白质表面展示以及 Epa1p 粘附素从细胞表面脱落。这项研究旨在证明重复拷贝数变异可以通过多种机制调节蛋白质功能，从而促进光滑念珠菌的致病性。