SUPPRESSION OF HYPHAL MORPHOGENESIS IN THE FUNGAL PATHOGEN C. ALBICANS

Candida albicans is a human commensal microorganism that can cause life-threatening systemic infections in immunocompromised individuals. A significant virulence trait of C. albicans is its ability to undergo transition between yeast and hyphal (filamentous) morphologies. The hyphal switch allows effective invasion of host tissues, and confers the ability to form biofilms and to block an adaptive immune response. Thus the suppression of hyphal morphogenesis is of both fundamental and therapeutic importance.

In a screen for kinases able to suppress hyphal morphogenesis, we identified AKL1, whose homolog in baker’s yeast is involved in the regulation of endocytosis. We find that CaAKL1 overexpression suppresses hyphal morphogenesis, whereas deletion of this gene leads to a more filamentous morphology. CaAKL1overexpression suppressed fluid phase endocytosis while its knockout strain exhibited higher levels of endocytosis. Interestingly, CaAKL1regulation of endocytosis seems to be activated under hyphal inducing conditions and not yeast inducing conditions. Using a CaUME6 knockout strain, which is not filamentous even under hyphal inducing conditions, we show that CaAKL1will still inhibit endocytosis, thus suggesting that it affects endocytosis directly, rather than via inhibition of morphogenesis. AKL1 was suggested to inhibit endocytosis in S. cerevisiae via phosphorylation of the endocytic protein Pan1. In C. albicans, overexpression of CaPAN1 suppressed the inhibition of morphogenesis by CaAKL1 overexpression. Western blotting analysis revealed an accelerated migration of CaPan1 in the absence of CaAkl1, consistent with reduced phosphorylation. Our results highlight the importance of the little-studied role of endocytosis in hyphal morphogenesis and suggests that CaAKL1 may inhibit filamentation through targeting of CaPAN1.