Elevation of cell wall chitin via Ca 2+ 2+ –calcineurin‐mediated PKC signaling pathway maintains the viability of Candida albicans Candida albicans in the absence of β‐1,6‐glucan synthesis

摘要

Summary 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 chs3 Δ/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 Ca 2+ –calcineurin. Also, kre6 Δ/Δ skn1 Δ/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.