C. albicans exhibits a wide range of
morphological
phenotypes due to phenotypic switching and bud to hypha transition. The yeast-to-hyphae transition (filamentation) is a rapid process and induced by environmental factors. Phenotypic switching is spontaneous, happens at lower rates and in certain strains up to seven different phenotypes are known. The best studied switching mechanism is the white to opaque switching (an epigenetic process). Other systems have been described as well. Two systems (the high-frequency switching system and white to opaque switching) were discover by
David R. Soll and colleagues. Switching in
C. albicans is often, but not always, influenced by environmental conditions such as the level of CO2, anaerobic conditions, medium used and temperature. In its yeast form
C. albicans ranges from 10 to 12
microns. Spores can form on the pseudohyphae called
chlamydospores which survive when put in unfavorable conditions such as dry or hot seasons.
Yeast-to-hypha switching Although often referred to as
dimorphic,
C. albicans is, in fact,
polyphenic (often also referred to as
pleomorphic). When cultured in standard yeast laboratory medium,
C. albicans grows as ovoid "yeast" cells. However, mild environmental changes in temperature, CO2, nutrients and pH can result in a morphological shift to filamentous growth. Filamentous cells share many similarities with yeast cells. Both cell types seem to play a specific, distinctive role in the survival and pathogenicity of
C. albicans. Yeast cells seem to be better suited for the dissemination in the bloodstream while hyphal cells have been proposed as a virulence factor. Hyphal cells are invasive and speculated to be important for tissue penetration, colonization of organs and surviving plus escaping macrophages. The transition from yeast to hyphal cells is termed to be one of the key factors in the virulence of
C. albicans; however, it is not deemed necessary. When
C. albicans cells are grown in a medium that mimics the physiological environment of a human host, they grow as filamentous cells (both true hyphae and pseudohyphae).
C. albicans can also form
chlamydospores, the function of which remains unknown, but it is speculated they play a role in surviving harsh environments as they are most often formed under unfavorable conditions. The cAMP-PKA signaling cascade is crucial for the morphogenesis and an important transcriptional regulator for the switch from yeast like cells to filamentous cells is EFG1.
High-frequency switching Besides the well-studied yeast-to-hyphae transition other switching systems have been described. One such system is the "high-frequency switching" system. During this switching different cellular morphologies (
phenotypes) are generated spontaneously. This type of switching does not occur en masse, represents a variability system and it happens independently from environmental conditions. In many 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. Being able to switch through so many different (morphological) phenotypes makes
C. albicans able to grow in different environments, both as a commensal and as a pathogen.
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. How
SIR2 itself is regulated in
S. cerevisiae may yet provide more clues as to the switching mechanisms of
C. albicans.
White-opaque switching Next to the
dimorphism and the first described high-frequency switching system
C. albicans undergoes another high-frequency switching process called white-opaque switching, which is another
phenotypic switching process in
C. albicans. It was the second high-frequency switching system discovered in
C. albicans. Phenotypic switching is often used to refer to white-opaque switching, which consists of two phases: one that grows as round cells in smooth, white colonies (referred to as white form) and one that is rod-like and grows as flat, gray colonies (called opaque form). This switch between white cells and opaque cells is important for the virulence and the
mating process of
C. albicans as the opaque form is the
mating competent form, being a million times more efficient in mating compared to the white type. This switching between white and opaque form is regulated by the WOR1 regulator (White to Opaque Regulator 1) which is controlled by the
mating type locus (MTL) repressor (a1-α2) that inhibits the expression of WOR1. Besides the white and opaque phase there is also a third one: the gray phenotype. This phenotype shows the highest ability to cause cutaneous infections. The white, opaque, and gray phenotypes form a phenotypic switching system where white cells switch to and from the opaque phase, white cells can irreversibly switch to the gray phase, and both white and gray cells can switch to and from the opaque/an opaque-like phase, respectively. Since it is often difficult to differentiate between white, opaque and gray cells phloxine B, a dye, can be added to the medium. Glucose starvation causes an increase in
intracellular reactive oxygen. This stress can lead to mating between two individuals of the same mating type, an interaction that may be frequent in nature under stressful conditions. ==Role in disease==