Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans
Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans
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DOI：
10.1128/iai.68.2.518-525.2000
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发表时间：
2000-02-01
影响因子：
3.1
通讯作者：
Calderone, R
中科院分区：
文献类型：
--
作者：
Calera, JA;Zhao, XJ;Calderone, R
在之前的研究中，我们报道了白色念珠菌双组分反应调节基因SSK1的分离和鉴定。该基因是酿酒酵母SSK1和裂殖酵母MCS4(+)基因的结构上的同源物，而不是功能上的同源物。在本研究中，我们构建了白色念珠菌的Delta ssk1突变体，并对其进行了表型鉴定。这一结果证实了我们之前的观察，即CaSSK1不同于SSK1或MCS4(+)，不调节细胞对渗透压或氧化应激的反应。相反，Delta ssk1缺失菌株在血清琼脂上菌丝形成严重减少，在其他固体培养基上菌丝发育完全缺陷，如199(pH 7.5)和Spider培养基上。相反，在固体培养基上氮素利用率低的条件下，Delta ssk1缺失菌株戏剧性地超侵袭琼脂，然而，当在类似于野生型的液体培养基中形成芽管和菌丝时，Delta ssk1缺失菌株以类似于Delta Chk1双组分组氨酸激酶突变体的方式絮凝，我们前面已经描述过。最后，毒力研究表明SSk1在白色念珠菌的发病机制中是必不可少的，这表明Ssk1p反应调节因子可能是抗真菌治疗的良好靶点。
In a previous study, we reported the isolation and characterization of the two-component response regulator SSK1 gene of Candida albicans. This gene is a structural but not a functional homolog of the SSK1 and mcs4(+) genes of Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. In the present study, we have constructed and phenotypically characterized Delta ssk1 mutants of C. albicans. The results confirmed our previous observation that CaSSK1, unlike SSK1 or mcs4(+), does not regulate cellular responses to either osmotic or oxidative stress. Instead, Delta ssk1 null strains showed severely reduced hyphal formation on serum agar and were totally defective in hyphal development on other solid media, such as medium 199 (pH 7.5) and Spider medium. In contrast, under conditions of low nitrogen availability on solid media, Delta ssk1 null strains dramatically hyperinvaded the agar, However, while forming germ tubes and hyphae in liquid media similar to those of the wild type, Delta ssk1 null strains flocculated in a manner similar to that of Delta chk1 two-component histidine kinase mutants, which we have previously described. Finally, virulence studies indicated that SSk1 is essential for the pathogenesis of C. albicans, suggesting that the Ssk1p response regulator could be a good target for antifungal therapy.