Candida Albicans - Dimorphism

Dimorphism

Although often referred to as "dimorphic", C. albicans is in fact polyphenic. When cultured in standard yeast laboratory medium, C. albicans grows as ovoid "yeast" cells. However, mild environmental changes in temperature and pH can result in a morphological shift to pseudohyphal growth. Pseudohyphae share many similarities with yeast cells, but their role during candidiasis remains unknown. When C. albicans cells are grown in a medium that mimics the physiological environment of a human host, they grow as "true" hyphae. Its ability to form hyphae has been proposed as a virulence factor, as these structures are often observed invading tissue, and strains that are unable to form hyphae are defective in causing infection.

In a process that superficially resembles dimorphism, C. albicans undergoes a process called phenotypic switching, in which different cellular morphologies are generated spontaneously. Of the classically studied strains, one that undergoes phenotypic switching is WO-1, which consists of two phases: one that grows as round cells in smooth, white colonies and one that is rod-like and grows as flat, gray colonies. The other strain known to undergo switching is 3153A; this strain produces at least seven different colony morphologies. In both the WO-1 and 3153A strains, the different phases convert spontaneously to the other(s) at a low frequency. The switching is reversible, and colony type can be inherited from one generation to another. While several genes that are expressed differently in different colony morphologies have been identified, some recent efforts focus on what might control these changes. Further, whether a potential molecular link between dimorphism and phenotypic switching occurs is a tantalizing question.

In the 3153A strain, a gene called SIR2 (for silent information regulator), which seems to be important for phenotypic switching, has been found. SIR2 was originally found in Saccharomyces cerevisiae (brewer's yeast), where it is involved in chromosomal silencing—a form of transcriptional regulation, in which regions of the genome are reversibly inactivated by changes in chromatin structure (chromatin is the complex of DNA and proteins that make chromosomes). In yeast, genes involved in the control of mating type are found in these silent regions, and SIR2 represses their expression by maintaining a silent-competent chromatin structure in this region. The discovery of a C. albicans SIR2 implicated in phenotypic switching suggests it, too, has silent regions controlled by SIR2, in which the phenotype-specific genes may reside.

Another potential regulatory molecule is Efg1p, a transcription factor found in the WO-1 strain that regulates dimorphism, and more recently has been suggested to help regulate phenotypic switching. Efg1p is expressed only in the white and not in the gray cell-type, and overexpression of Efg1p in the gray form causes a rapid conversion to the white form.

So far, very few data sugget dimorphism and phenotypic switching use common molecular components. However, it is not inconceivable that phenotypic switching may occur in response to some change in the environment, as well as being a spontaneous event. How SIR2 itself is regulated in S. cerevisiae may yet provide clues as to the switching mechanisms of C. albicans.