Abstract

The fungal pathogen Candida albicans differentiates between yeast, hyphae and pseudohyphae in order to enhance survival in the human host. Environmental cues induce hyphal development and expression of hyphal-specific genes. Filaments also result from yeast cell cycle arrest, but the nature of these cells and their mechanisms of formation are less clear. We previously demonstrated that depletion of the mitotic polo-like kinase Cdc5p resulted in the production of filaments under yeast growth conditions that were distinct from hyphae with respect to several criteria, yet expressed hyphal-specific genes at later stages of development. In order to clarify the identity of these growth forms and their relationship to true hyphae, we conducted time course-based investigations of aspects of the polar growth machinery, which can distinguish cell types. During later stages of Cdc5p depletion, the myosin light chain Mlc1p demonstrated a Spitzenkörper-like localization in the tips of some filaments, and the Cdc42p GAP Rga2p became hyper-phosphorylated, as in true hyphae. Hyphal-specific genes HWP1, UME6 and HGC1 were strongly expressed at approximately the same time. HWP1 expression was dependent on Ume6p, and absence of Ume6p or Hgc1p influenced late-stage filament morphology and integrity. Finally, polarized growth and UME6 expression in Cdc5p-depleted cells were independent of the transcription factor Hms1p. Thus, depleting Cdc5p generates elongated buds that switch to a hyphal fate over time through a mechanism that involves UME6 and HGC1 induction, possibly in response to maintenance of polarized growth. The results expand on the multiple strategies with which C. albicans can modulate growth mode and expression of virulence determinants.