Bistable Expression of WOR1, a Master Regulator of White-opaque Switching in Candida Albicans

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Aug 15

PMID 16905649

Citations 174

Authors

Guanghua Huang

Huafeng Wang

Song Chou

Xinyi Nie

Jiangye Chen

Haoping Liu

Affiliations

Soon will be listed here.

Abstract

Candida albicans, a commensal organism and a pathogen of humans, can switch stochastically between a white phase and an opaque phase without an intermediate phase. The white and opaque phases have distinct cell shapes and gene expression programs. Once switched, each phase is stable for many cell divisions. White-opaque switching is under a1-alpha2 repression and therefore only happens in a or alpha cells. Mechanisms that control the switching are unknown. Here, we identify Wor1 (white-opaque regulator 1) as a master regulator of white-opaque switching. The deletion of WOR1 blocks opaque cell formation. The ectopic expression of WOR1 converts all cells to stable opaque cells in a or alpha cells. In addition, the ectopic expression of WOR1 in a/alpha cells is sufficient to induce opaque cell formation. Importantly, WOR1 expression displays an all-or-none pattern. It is undetectable in white cells, and it is highly expressed in opaque cells. The ectopic expression of Wor1 induces the transcription of WOR1 from the WOR1 locus, which correlates with the switch to opaque phase. We present genetic evidence for feedback regulation of WOR1 transcription. The feedback regulation explains the bistable and stochastic nature of white-opaque switching.

Citing Articles

Transcriptomic atlas of the morphologic development of the fungal pathogen reveals key phase-enriched transcripts.

Homer C, Voorhies M, Walcott K, Ochoa E, Sil A bioRxiv. 2024; .

PMID: 39463982 PMC: 11507689. DOI: 10.1101/2024.10.13.618122.

The rod cell, a small form of , possesses superior fitness to the host gut and adaptation to commensalism.

Xu Y, Zhu W, Dai B, Xiao H, Chen J Acta Biochim Biophys Sin (Shanghai). 2024; 56(9):1278-1288.

PMID: 38887798 PMC: 11532210. DOI: 10.3724/abbs.2024066.

Genotypic diversity, virulence, and molecular genetic tools in .

Sepulveda V, Goldman W, Matute D Microbiol Mol Biol Rev. 2024; 88(2):e0007623.

PMID: 38819148 PMC: 11332355. DOI: 10.1128/mmbr.00076-23.

White-opaque switching in : cell biology, regulation, and function.

Soll D Microbiol Mol Biol Rev. 2024; 88(2):e0004322.

PMID: 38546228 PMC: 11332339. DOI: 10.1128/mmbr.00043-22.

Variation in transcription regulator expression underlies differences in white-opaque switching between the SC5314 reference strain and the majority of Candida albicans clinical isolates.

Lohse M, Ziv N, Johnson A Genetics. 2023; 225(3).

PMID: 37811798 PMC: 10627253. DOI: 10.1093/genetics/iyad162.

References

GARDNER T, Cantor C, Collins J . Construction of a genetic toggle switch in Escherichia coli. Nature. 2000; 403(6767):339-42. DOI: 10.1038/35002131. View

Bennett R, Johnson A . Mating in Candida albicans and the search for a sexual cycle. Annu Rev Microbiol. 2005; 59:233-55. DOI: 10.1146/annurev.micro.59.030804.121310. View

Becskei A, Seraphin B, Serrano L . Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J. 2001; 20(10):2528-35. PMC: 125456. DOI: 10.1093/emboj/20.10.2528. View

Hazan I, Liu H . Hyphal elongation is regulated independently of cell cycle in Candida albicans. Mol Biol Cell. 2002; 13(1):134-45. PMC: 65078. DOI: 10.1091/mbc.01-03-0116. View

Ferrell Jr J . Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol. 2002; 14(2):140-8. DOI: 10.1016/s0955-0674(02)00314-9. View

Miller M, Johnson A . White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell. 2002; 110(3):293-302. DOI: 10.1016/s0092-8674(02)00837-1. View

Lan C, Newport G, Murillo L, Jones T, Scherer S, Davis R . Metabolic specialization associated with phenotypic switching in Candidaalbicans. Proc Natl Acad Sci U S A. 2002; 99(23):14907-12. PMC: 137518. DOI: 10.1073/pnas.232566499. View

Chen J, Chen J, Lane S, Liu H . A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol Microbiol. 2002; 46(5):1335-44. DOI: 10.1046/j.1365-2958.2002.03249.x. View

Magee B, Legrand M, Alarco A, Raymond M, Magee P . Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol Microbiol. 2002; 46(5):1345-51. DOI: 10.1046/j.1365-2958.2002.03263.x. View

10.

Soll D, Lockhart S, Zhao R . Relationship between switching and mating in Candida albicans. Eukaryot Cell. 2003; 2(3):390-7. PMC: 161441. DOI: 10.1128/EC.2.3.390-397.2003. View

11.

Bennett R, Uhl M, Miller M, Johnson A . Identification and characterization of a Candida albicans mating pheromone. Mol Cell Biol. 2003; 23(22):8189-201. PMC: 262406. DOI: 10.1128/MCB.23.22.8189-8201.2003. View

12.

Tsong A, Miller M, Raisner R, Johnson A . Evolution of a combinatorial transcriptional circuit: a case study in yeasts. Cell. 2003; 115(4):389-99. DOI: 10.1016/s0092-8674(03)00885-7. View

13.

Panwar S, Legrand M, Dignard D, Whiteway M, Magee P . MFalpha1, the gene encoding the alpha mating pheromone of Candida albicans. Eukaryot Cell. 2003; 2(6):1350-60. PMC: 326654. DOI: 10.1128/EC.2.6.1350-1360.2003. View

14.

Slutsky B, Staebell M, Anderson J, Risen L, Pfaller M, Soll D . "White-opaque transition": a second high-frequency switching system in Candida albicans. J Bacteriol. 1987; 169(1):189-97. PMC: 211752. DOI: 10.1128/jb.169.1.189-197.1987. View

15.

Anderson J, Soll D . Unique phenotype of opaque cells in the white-opaque transition of Candida albicans. J Bacteriol. 1987; 169(12):5579-88. PMC: 213989. DOI: 10.1128/jb.169.12.5579-5588.1987. View

16.

Rikkerink E, Magee B, Magee P . Opaque-white phenotype transition: a programmed morphological transition in Candida albicans. J Bacteriol. 1988; 170(2):895-9. PMC: 210739. DOI: 10.1128/jb.170.2.895-899.1988. View

17.

Srikantha T, Soll D . A white-specific gene in the white-opaque switching system of Candida albicans. Gene. 1993; 131(1):53-60. DOI: 10.1016/0378-1119(93)90668-s. View

18.

Liu H, Styles C, Fink G . Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Science. 1993; 262(5140):1741-4. DOI: 10.1126/science.8259520. View

19.

Kunitomo H, Sugimoto A, Wilkinson C, Yamamoto M . Schizosaccharomyces pombe pac2+ controls the onset of sexual development via a pathway independent of the cAMP cascade. Curr Genet. 1995; 28(1):32-8. DOI: 10.1007/BF00311879. View

20.

Liu H, Styles C, Fink G . Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth. Genetics. 1996; 144(3):967-78. PMC: 1207636. DOI: 10.1093/genetics/144.3.967. View