Examining morphological transitioning in Candida albicans through the modulation of FKH2

Candida albicans, a human pathogenic fungus, has the ability to transition between three principal morphologies in response to environmental cues: yeast, pseudohyphae, and true hyphae. Previous research shows that the yeast-to-pseudohyphae and yeast-to-hyphae transitions are reversible. What is unclear is whether C. albicans pseudohyphae must first revert to yeast before becoming hypha. A recent study in this lab with a tetracycline-regulatable tet-RFG1 strain suggested that pseudohyphal cells revert back to yeast before transitioning to hyphae. C. albicans morphological flexibility allows it to persist in a wide range of host niches and the yeast-to-hyphae transition is believed to be a requisite virulence factor. The elucidation of the complex mechanisms behind these transitioning phenomena will hasten our pursuit of more effective drug targets in the treatment of disease.

In this study, we describe the production, characterization, and use of a novel fkh2Delta-tetFKH2 strain to investigate C. albicans morphological transitioning. Fkh2p is an important cell cycle transcription factor and the null mutant grows constitutively as pseudohyphae. A single tet-regulatable copy of FKH2 inserted at the RP10 locus allows the tight regulation of FKH2 expression in the presence or absence of the tetracycline derivative doxycycline. This regulatable allele gives us the opportunity to grow Candida albicans as pseudohyphae by depleting FKH2 and examining hyphal induction as Fkh2p is restored.