Regulator Of White-opaque Switching Research Articles

Hbr1 Activates and Represses Hyphal Growth in Candida albicans and Regulates Fungal Morphogenesis under Embedded Conditions.

Transitions between yeast and hyphae are essential for Candida albicans pathogenesis. The genetic programs that regulate its hyphal development can be distinguished by embedded versus aerobic surface agar invasion. Hbr1, a regulator of white-opaque switching, is also a positive and negative regulator of hyphal invasion. During embedded growth at 24°C, an HBR1/hbr1 strain formed constitutively filamentous colonies throughout the matrix, resembling EFG1 null colonies, and a subset of long unbranched hyphal aggregates enclosed in a spindle-shaped capsule. Inhibition of adenylate cyclase with farnesol perturbed the filamentation of HBR1/hbr1 cells producing cytokinesis-defective hyphae whereas farnesol treated EFG1 null cells produced abundant opaque-like cells. Point mutations in the Hbr1 ATP-binding domain caused distinct filamentation phenotypes including uniform radial hyphae, hyphal sprouts, and massive yeast cell production. Conversely, aerobic surface colonies of the HBR1 heterozygote on Spider and GlcNAc media lacked filamentation that could be rescued by growth under low (5%) O2. Consistent with these morphogenesis defects, the HBR1 heterozygote exhibited attenuated virulence in a mouse candidemia model. These data define Hbr1 as an ATP-dependent positive and negative regulator of hyphal development that is sensitive to hypoxia.

The zinc-finger transcription factor, Ofi1, regulates white–opaque switching and filamentation in the yeast <italic>Candida albicans</italic>

Candida albicans is a major fungal pathogen of humans. The most striking biological feature of C. albicans is its phenotypic plasticity, allowing it to undergo morphological transitions in response to various environmental cues. Transcription factors play critical roles in the regulation of morphological transitions. Here, we report the role of opaque and filamentation inducer 1 (Ofi1), a previously uncharacterized zinc-finger-containing protein encoded by the gene orf19.4972, in the regulation of white-opaque switching and filamentous growth. Over-expression of OFI1 not only induced white-to-opaque switching but also promoted filamentation and invasive growth in C. albicans. Deletion of OFI1 had no obvious effect on filamentation under the culture conditions tested, while deletion of OFI1 reduced the frequency of white-to-opaque switching. We propose that Ofi1 functions downstream of Wor1, the master regulator of white-opaque switching. However, over-expression of OFI1 in the wor1/wor1 mutant could not induce the opaque phenotype, suggesting that Ofi1 does not work alone and other transcription factors downstream of Wor1 are also involved in this regulation. Given the importance of Ofi1 in the regulation of white-opaque switching and filamentation, the present study establishes a new link between these two processes.

Candida albicans Zcf37, a zinc finger protein, is required for stabilization of the white state

Candida albicans, the most prevalent human fungal pathogen, can switch stochastically between white and opaque phases. In this study, we identified Zcf37, a zinc finger protein, as a new regulator of white-opaque switching. Deletion of ZCF37 increased white-to-opaque switching frequency and stabilized the opaque state. Overexpression of ZCF37 promoted conversion of opaque cells to white phase, but needed existence of Efg1, a key regulator required for maintenance of the white state. Deletion of EFG1 abolished the effect of ectopically expressed Zcf37 on opaque-to-white switching, whereas ectopic expression of EFG1 promoted white cell formation without presence of Zcf37. Our results suggest that Zcf37 acts as an activator of white cell formation and a repressor of opaque state and functions upstream of Efg1.