Elevation of cell wall chitin via Ca2+ -calcineurin-mediated PKC signaling pathway maintains the viability of Candida albicans in the absence of β-1,6-glucan synthesis.

Abstract

β-1,6-glucan is an important cell wall component of Candida albicans. Deleted mutants of the two β-1,6-glucan synthase genes KRE6 and SKN1 are viable albeit with a range of defects including slow growth. It remains unclear whether β-1,6-glucan synthesis is not required under culture conditions or compensatory mechanisms exist in C. albicans. Here, we report that depleting β-1,6-glucan synthases leads to a significant increase in cell wall chitin levels through the posttranscriptional regulation of the chitin synthase Chs3 which maintains cell viability. And depleting β-1,6-glucan synthases in chs3Δ/Δ cells results in cell death. The elevation of cell wall chitin is mediated by the activation of the PKC signaling pathway and an unknown pathway(s) involving Ca2+ -calcineurin. Also, kre6Δ/Δ skn1Δ/Δ cells are not more susceptible to caspofungin, the antifungal drug that inhibits β-1,3-glucan synthases, suggesting that β-1,3-glucan has no role in compensating β-1,6-glucan synthesis. Given the vital importance of elevating chitin synthesis in the absence of β-1,6-glucan synthesis in C. albicans, antifungal drugs targeting β-1,6-glucan and chitin synthesis could be used in combination therapies.