title: White-opaque switching in natural MTLa/α isolates of Candida albicans: evolutionary implications for roles in host adaptation, pathogenesis, and sex.
abstract: Phenotypic transitions play critical roles in host adaptation, virulence, and sexual reproduction in pathogenic fungi. A minority of natural isolates of Candida albicans, which are homozygous at the mating type locus (MTL, a/a or α/α), are known to be able to switch between two distinct cell types: white and opaque. It is puzzling that white-opaque switching has never been observed in the majority of natural C. albicans strains that have heterozygous MTL genotypes (a/α), given that they contain all of the opaque-specific genes essential for switching. Here we report the discovery of white-opaque switching in a number of natural a/α strains of C. albicans under a condition mimicking aspects of the host environment. The optimal condition for white-to-opaque switching in a/α strains of C. albicans is to use N-acetylglucosamine (GlcNAc) as the sole carbon source and to incubate the cells in 5% CO2. Although the induction of white-to-opaque switching in a/α strains of C. albicans is not as robust as in MTL homozygotes in response to GlcNAc and CO2, opaque cells of a/α strains exhibit similar features of cellular and colony morphology to their MTL homozygous counterparts. Like MTL homozygotes, white and opaque cells of a/α strains differ in their behavior in different mouse infection models. We have further demonstrated that the transcriptional regulators Rfg1, Brg1, and Efg1 are involved in the regulation of white-to-opaque switching in a/α strains. We propose that the integration of multiple environmental cues and the activation and inactivation of a set of transcriptional regulators controls the expression of the master switching regulator WOR1, which determines the final fate of the cell type in C. albicans. Our discovery of white-opaque switching in the majority of natural a/α strains of C. albicans emphasizes its widespread nature and importance in host adaptation, pathogenesis, and parasexual reproduction.
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Nobile
authors.forename: Yaojun
authors.initials: Y
authors.lastname: Tong
authors.forename: Guobo
authors.initials: G
authors.lastname: Guan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Chengjun
authors.initials: C
authors.lastname: Cao
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Hernday
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Bai
authors.forename: Guanghua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015152:Blotting, Northern; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D049770:Genes, Mating Type, Fungal / Q000235:genetics / Q000502:physiology; D005838:Genotype; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics
chemical_list: D005656:Fungal Proteins
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