HWP1 Functions in the Morphological Development of Candida albicans Downstream of EFG1, TUP1, and RBF1

The morphological plasticity of Candida albicans is an important determinant of pathogenicity, and nonfilamentous mutants are avirulent. HWP1, a hypha-specific gene, was identified in a genetic screen for developmentally regulated genes and encodes a cell surface protein of unknown function. Heterozygous and homozygous deletions of HWP1 resulted in a medium-conditional defect in hyphal development. HWP1 expression was blocked in a Δefg1 mutant, reduced in an Δrbf1 mutant, and derepressed in a Δtup1 mutant. Therefore, HWP1 functions downstream of the developmental regulators EFG1, TUP1, and RBF1. Mutation of CPH1 had no effect on HWP1 expression, suggesting that the positive regulators of hyphal development, CPH1 and EFG1, are components of separate pathways with different target genes. The expression of a second developmentally regulated gene, ECE1, was similarly regulated by EFG1. Since ECE1 is not required for hyphal development, the regulatory role of EFG1 apparently extends beyond the control of cell shape determinants. However, expression of ECE1 was not influenced by TUP1, suggesting that there may be some specificity in the regulation of morphogenic elements during hyphal development.

白色念珠菌（Candida albicans）的形态可塑性是其致病性的重要决定因素，无丝状突变株不具备致病性。菌丝特异性基因HWP1是通过发育调控基因遗传筛选鉴定得到的，其编码一种功能未知的细胞表面蛋白。对HWP1进行杂合缺失与纯合缺失后，菌株出现了培养基依赖性的菌丝发育缺陷。HWP1的表达在Δefg1突变株中被阻断，在Δrbf1突变株中被下调，而在Δtup1突变株中发生去阻遏。因此，HWP1处于发育调控因子EFG1、TUP1和RBF1的下游。CPH1的突变对HWP1的表达无影响，这表明菌丝发育的正向调控因子CPH1与EFG1分属两条不同的信号通路，且各自拥有不同的靶基因。另一发育调控基因ECE1的表达同样受EFG1调控。鉴于ECE1并非菌丝发育所必需，EFG1的调控功能显然超出了对细胞形态决定因子的调控范围。不过，TUP1对ECE1的表达并无影响，这提示在菌丝发育过程中，形态发生相关元件的调控或许存在一定特异性。