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Bcr1 plays a central role in the regulation of opaque cell filamentation in Candida albicans.

ABSTRACT: The human fungal pathogen Candida albicans has at least two types of morphological transitions: white to opaque cell transitions and yeast to hyphal transitions. Opaque cells have historically not been known to undergo filamentation under standard filament-inducing conditions. Here we find that Bcr1 and its downstream regulators Cup9, Nrg1 and Czf1 and the cAMP-signalling pathway control opaque cell filamentation in C.?albicans. We have shown that deletion of BCR1, CUP9, NRG1 and CZF1 results in opaque cell filamentation under standard culture conditions. Disruption of BCR1 in white cells has no obvious effect on hyphal growth, suggesting that Bcr1 is an opaque-specific regulator of filamentation under the conditions tested. Moreover, inactivation of the cAMP-signalling pathway or disruption of its downstream transcriptional regulators, FLO8 and EFG1, strikingly attenuates filamentation in opaque cells of the bcr1/bcr1 mutant. Deletion of HGC1, a downstream gene of the cAMP-signalling pathway encoding G1 cyclin-related protein, completely blocks opaque cell filamentation induced by inactivation of BCR1. These results demonstrate that Bcr1 regulated opaque cell filamentation is dependent on the cAMP-signalling pathway. This study establishes a link between the white-opaque switch and the yeast-filamentous growth transition in C.?albicans.

SUBMITTER: Guan G

PROVIDER: S-EPMC3758918 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Bcr1 plays a central role in the regulation of opaque cell filamentation in Candida albicans.

Guan Guobo G Xie Jing J Tao Li L Nobile Clarissa J CJ Sun Yuan Y Cao Chengjun C Tong Yaojun Y Huang Guanghua G

Molecular microbiology 20130712 4

The human fungal pathogen Candida albicans has at least two types of morphological transitions: white to opaque cell transitions and yeast to hyphal transitions. Opaque cells have historically not been known to undergo filamentation under standard filament-inducing conditions. Here we find that Bcr1 and its downstream regulators Cup9, Nrg1 and Czf1 and the cAMP-signalling pathway control opaque cell filamentation in C. albicans. We have shown that deletion of BCR1, CUP9, NRG1 and CZF1 results in ...[more]

PMID: 23808664

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Project description:During induced differentiation, the process often involves a commitment event, after which induced cells, when returned to noninducing conditions, continue to differentiate. The commitment event is rarely identified. Candida albicans differentiates from the white to opaque phenotype, a prerequisite for mating and a process accompanying colonization of the lower gastrointestinal tract and skin. In analyses of white cell populations induced to synchronously differentiate from the white to opaque phenotype, opaque commitment occurs at approximately the same time as evagination and chitin ring formation in the process of daughter cell formation, several hours after the master switch gene WOR1 is upregulated. Mutational analyses of transcription factor binding regions P1, P2, P3, P4, and P6 of the WOR1 promoter reveal that individual deletion of any of the five transcription factor binding regions does not eliminate morphological differentiation to the opaque cell phenotype under opaque-inducing conditions, but individual deletion of P2, P3, or P4, blocks opaque commitment and maintenance of the opaque phenotype after transition to noninducing conditions. These results suggest that commitment occurs at the level of the WOR1 promoter and that morphological differentiation can be dissociated from phenotypic commitment. IMPORTANCE Candida albicans, the most pervasive fungal pathogen colonizing humans, undergoes a phenotypic transition between a white and opaque phenotype. The unique opaque phenotype is necessary for mating and colonization of the lower gastrointestinal tract. Wor1, a transcription factor (TF), plays a central role in activating this transition. Under physiological conditions that induce mass conversion from white to opaque in vitro, cells commit to the opaque phenotype at the time of evagination to form a daughter cell, but several hours after upregulation of WOR1 expression. By analyzing deletion derivatives of the WOR1 promoter, we demonstrate that three of five regulatory regions of WOR1 that bind TFs involved with the regulation of the phenotypic switch are individually required for commitment to the opaque phenotype, but are not necessary for expressing the opaque phenotype. These results demonstrate that morphological differentiation can be dissociated from phenotypic commitment and that commitment occurs at the level of the WOR1 promoter.

Dataset Information

Bcr1 plays a central role in the regulation of opaque cell filamentation in Candida albicans.

Publications

Bcr1 plays a central role in the regulation of opaque cell filamentation in Candida albicans.

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