All Mating Type Locus strain types of Candida albicans show white-opaque switching competency, not just MTL homozygotes, which allows them to adapt better to environmental changes.
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% CO 2. 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 CO 2, 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.
Phenotypic transitions enable fungal pathogens to better adapt to their ever-changing environments. Approximately 10% of natural Candida albicans strains, which are homozygous at the mating type locus ( MTL, a/ a and α/α), can switch between two distinguishable morphological forms: white and opaque. The two cell types differ in a number of biological aspects including virulence, susceptibility to host immune attacks, and mating competency. Here, we demonstrate that white-opaque switching competency is not restricted to the MTL homozygous strains, but is a general characteristic of all MTL strain types of C. albicans ( a/ a, α/α, and a/α). Two host environmental cues, N-acetylglucosamine and CO 2, promote white-to-opaque switching and stabilize the opaque phenotype. Thus, although switching is normally blocked in a/α cells, this block can be overcome through specific environmental changes. We further show that three transcriptional regulators (Rfg1, Brg1, and Efg1) help to regulate white-opaque switching in MTL heterozygotes of C. albicans. This study generalizes white-opaque switching to strains with all mating-type configurations and emphasizes its importance in host adaptation, pathogenesis, and parasexual reproduction.