A G₁ Cyclin Is Necessary for Maintenance of Filamentous Growth in Candida albicans

Abstract

Candida albicans undergoes a dramatic morphological transition in response to various growth conditions. This ability to switch from a yeast form to a hyphal form is required for its pathogenicity. The intractability of Candida to traditional genetic approaches has hampered the study of the molecular mechanism governing this developmental switch. Our approach is to use the more genetically tractable yeast Saccharomyces cerevisiae to yield clues about the molecular control of filamentation for further studies in Candida. G₁ cyclins Cln1 and Cln2 have been implicated in the control of morphogenesis in S. cerevisiae. We show that C. albicans CLN1(CaCLN1) has the same cell cycle-specific expression pattern as CLN1 and CLN2 of S. cerevisiae. To investigate whether G₁ cyclins are similarly involved in the regulation of cell morphogenesis during the yeast-to-hypha transition of C. albicans, we mutated CaCLN1. Cacln1/Cacln1 cells were found to be slower than wild-type cells in cell cycle progression. The Cacln1/Cacln1 mutants were also defective in hyphal colony formation on several solid media. Furthermore, while mutant strains developed germ tubes under several hypha-inducing conditions, they were unable to maintain the hyphal growth mode in a synthetic hypha-inducing liquid medium and were deficient in the expression of hypha-specific genes in this medium. Our results suggest that CaCln1 may coordinately regulate hyphal development with signal transduction pathways in response to various environmental cues.

ACKNOWLEDGMENTS

We thank C. E. Birse for helpful discussions, S. B. Sandmeyer for comments on the manuscript, and anonymous reviewers for thoughtful critiques. We also thank W. Fonzi and J. F. Ernst for reagents.

This work was supported by NIH grant GM-55155 and by UC Universitywide AIDS Research Program grant K96-I-016 to H. Liu. H. Liu is a new investigator of Burroughs Wellcome Fund.