Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans

In a previous study, we reported the isolation and characterization of the two-component response regulator SSK1 gene of Candida albicans. This gene i s a structural but not a functional homolog of the SSK1 and mcs4(+) genes o f Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. In the present study, we have constructed and phenotypically characterized Del ta ssk1 mutants of C. albicans. The results confirmed our previous observat ion that CaSSK1, unlike SSK1 or mcs4(+), does not regulate cellular respons es to either osmotic or oxidative stress. Instead, Delta ssk1 null strains showed severely reduced hyphal formation on serum agar and were totally def ective in hyphal development on other solid media, such as medium 199 (pH 7 .5) and Spider medium. In contrast, under conditions of low nitrogen availa bility on solid media, Delta ssk1 null strains dramatically hyperinvaded th e agar, However, while forming germ tubes and hyphae in liquid media simila r to those of the wild type, Delta ssk1 null strains flocculated in a manne r similar to that of Delta chk1 two-component histidine kinase mutants, whi ch 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.