Defective Hyphal Development and Avirulence Caused by a Deletion of the SSK1 Response Regulator Gene in Candida albicans

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Abstract
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 Δ 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, Δ 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, Δ ssk1 null strains dramatically hyperinvaded the agar. However, while forming germ tubes and hyphae in liquid media similar to those of the wild type, Δ ssk1 null strains flocculated in a manner similar to that of Δ 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.