Negative Regulation of Filamentous Growth in Candida albicans by Dig1p

Candida albicans is an opportunistic fungal pathogen capable of causing superficial and systemic infections in humans. The ability of C. albicans to switch between various morphological forms depending on its host environment is thought to contribute to its virulence. Filamentous growth states are associated with tissue invasion, biofilm formation, evasion of innate host defences and mating. Although the mechanisms of activation of filamentous growth pathways are well understood, less is known about which factors control the negative regulation of filamentation. In this study, we have identified a previously uncharacterized Orf that shares sequence similarity with Saccharomyces cerevisiae Dig1p and Dig2p. Deletion of the gene encoding this Orf triggers invasive growth in C. albicans and so we have retained the yeast designation of Dig1 (for Down-regulation of Invasive Growth). Mutants lacking CaDIG1 form cultures of hyperpolarized cells, form robust biofilms, are highly invasive in vitro but not in vivo and are constitutively activated for the pheromone response. Deletion of key transcription factors that act downstream of Dig1p provide evidence to suggest that CaDig1 regulates filamentation and mating through multiple signalling pathways. Transcriptional analysis of the C. albicans dig1Δ/dig1Δ homozygous mutant versus the wild type (SN148) in the MTLa/alpha background. Four biological replicates of the mutant and the wild type were included in the analysis. Samples were grown at 30 °C in YPD medium plus uridine