Abstract
The human opportunistic pathogen Candida albicans undergoes a reversible morphological transition between the yeast and hyphal states in response to a variety of signals. One such environmental trigger is growth within a semisolid matrix such as agar medium. This growth condition is of interest because it may mimic the growth of C. albicans in contact with host tissue during infection. During growth within a semisolid matrix, hyphal growth is positively regulated by the transcriptional regulator Czf1p and negatively by a second key transcriptional regulator, Efg1p. Genetic studies indicate that Czf1p, a member of the zinc-cluster family of transcriptional regulators, exerts its function by opposing the inhibitory influence of Efg1p on matrix-induced filamentous growth. We examined the importance of the two known activities of Czf1p, DNA-binding and interaction with Efg1p. We found that the two activities were separable by mutation allowing us to demonstrate that the DNA-binding activity of Czf1p was essential for its role as a positive regulator of morphogenesis. Surprisingly, however, interactions with Efg1p appeared to be largely dispensable. Our studies provide the first evidence of a key role for the DNA-binding activity of Czf1p in the morphological yeast-to-hyphal transition triggered by matrix-embedded growth.
Highlights
Candida albicans is a diploid fungus that has adapted primarily for survival as a commensal of mammalian hosts
We separated the two known activities of Czf1p and showed that a DNA binding defect confers a czf1 mutant phenotype. These results provide the first evidence of a key role for the DNA-binding activity of Czf1p in regulating the morphological yeast-to-hyphal transition triggered by matrixembedded growth
A czf1 mutant, Czf1R321A, was defective during in vitro DNA-binding using a target sequence from the CZF1 promoter region. This mutant was defective in the yeast-tohyphal transition during matrix-embedded growth at 25uC
Summary
Candida albicans is a diploid fungus that has adapted primarily for survival as a commensal of mammalian hosts. Efg1p, required for filamentous growth at 37uC in a range of conditions, has a negative effect on this process during matrix-embedded growth at 25uC [14]. A czf1D mutant has a defect in filamentation during embedded growth but not during other liquid based hypha-inducing conditions pointing to the specific role of Czf1p in the control of matrix-induced filamentation [13]. The biological function of the protein’s DNA-binding activity and the significance of the Czf1p-Efg1p interaction in the control of matrix-induced filamentation have not been previously studied. We show that DNA-binding of Czf1p is essential for its regulatory function and role as a positive regulator of filamentation, whereas interaction with Efg1p is dispensable for this function
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