Brown Victoria, Sexton Jessica A, Johnston Mark
Department of Genetics, Center for Genome Sciences, Washington University School of Medicine, 4444 Forest Park Blvd., Rm. 5401, Campus Box 8510, St. Louis, MO 63108, USA.
Eukaryot Cell. 2006 Oct;5(10):1726-37. doi: 10.1128/EC.00186-06.
The Hgt4 protein of Candida albicans (orf19.5962) is orthologous to the Snf3 and Rgt2 glucose sensors of Saccharomyces cerevisiae that govern sugar acquisition by regulating the expression of genes encoding hexose transporters. We found that HGT4 is required for glucose induction of the expression of HGT12, HXT10, and HGT7, which encode apparent hexose transporters in C. albicans. An hgt4Delta mutant is defective for growth on fermentable sugars, which is consistent with the idea that Hgt4 is a sensor of glucose and similar sugars. Hgt4 appears to be sensitive to glucose levels similar to those in human serum ( approximately 5 mM). HGT4 expression is repressed by high levels of glucose, which is consistent with the idea that it encodes a high-affinity sugar sensor. Glucose sensing through Hgt4 affects the yeast-to-hyphal morphological switch of C. albicans cells: hgt4Delta mutants are hypofilamented, and a constitutively signaling form of Hgt4 confers hyperfilamentation of cells. The hgt4Delta mutant is less virulent than wild-type cells in a mouse model of disseminated candidiasis. These results suggest that Hgt4 is a high-affinity glucose sensor that contributes to the virulence of C. albicans.
白色念珠菌的Hgt4蛋白（orf19.5962）与酿酒酵母的Snf3和Rgt2葡萄糖传感器直系同源，后者通过调节编码己糖转运蛋白的基因表达来控制糖的摄取。我们发现，HGT4是白色念珠菌中葡萄糖诱导HGT12、HXT10和HGT7表达所必需的，这三个基因编码明显的己糖转运蛋白。hgt4Delta突变体在可发酵糖上生长存在缺陷，这与Hgt4是葡萄糖及类似糖的传感器这一观点相符。Hgt4似乎对与人类血清中相似的葡萄糖水平（约5 mM）敏感。HGT4的表达受到高浓度葡萄糖的抑制，这与它编码一种高亲和力糖传感器的观点一致。通过Hgt4进行的葡萄糖感应影响白色念珠菌细胞的酵母-菌丝形态转换：hgt4Delta突变体菌丝形成减少，而组成型信号形式的Hgt4使细胞菌丝过度形成。在播散性念珠菌病小鼠模型中，hgt4Delta突变体的毒力低于野生型细胞。这些结果表明，Hgt4是一种高亲和力葡萄糖传感器，对白色念珠菌的毒力有贡献。
