Candida albicans

Genome

One of the most important features of the C. albicans genome is the occurrence of numeric and structural chromosomal rearrangements as means of generating genetic diversity, named chromosome length polymorphisms (contraction/expansion of repeats), reciprocal translocations, chromosome deletions and trisomy of individual chromosomes. These karyotypic alterations lead to changes in the phenotype, which is an adaptation strategy of this fungus. These mechanisms will be better understood with the complete analysis of the C. albicans genome.

An unusual feature of the Candida genus is that in many of its species (including C. albicans and C. tropicalis, but not, for instance, C. glabrata) the CUG codon, which normally specifies leucine, specifies serine in these species. This is an unusual example of a departure from the standard genetic code, and most such departures are in start codons or, for eukaryotes, mitochondrial genetic codes. This alteration may, in some environments, help these Candida species by inducing a permanent stress response, a more generalized form of the heat shock response.

The genome of C. albicans is highly dynamic, and this variability has been used advantageously for molecular epidemiological studies and population studies in this species. The genome sequence has allowed for identifying the presence of a parasexual cycle (no detected meiotic division) in C. albicans. This study of the evolution of sexual reproduction in six Candida species found recent losses in components of the major meiotic crossover-formation pathway, but retention of a minor pathway. The authors suggested that if Candida species undergo meiosis it is with reduced machinery, or different machinery, and indicated that unrecognized meiotic cycles may exist in many species. In another evolutionary study, introduction of partial CUG identity redefinition (from Candida species) into Saccharomyces cerevisiae clones caused a stress response that negatively affected sexual reproduction. This CUG identity redefinition, occurring in ancestors of Candida species, was thought to lock these species into a diploid or polyploid state with possible blockage of sexual reproduction.

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. Candida albicans can also form chlamydospores, the function of which remains unknown.

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 suggest 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.

Heterozygosity

The heterozygosity of the Candida genome exceeds that found in other genomes and is widespread among clinical isolates. Nonsynonymous single-base polymorphisms result in two proteins that differ in one or several amino acids that may confer functional differences for each protein. This situation considerably increases the number of different proteins encoded by the genome.

Hwp1

Hwp1 stands for Hyphal wall protein 1. Hwp1 is a mannoprotein located on the surface of the hyphae in the hyphal form of Candida albicans. Hwp1 is a mammalian transglutaminase substrate. This host enzyme allows Candida albicans to attach stably to host epithelial cells. Adhesion of Candida albicans to host cells is an essential first step in the infection process for colonization and subsequent induction of mucosal infection.

Slr1

RNA-binding protein Slr1 was recently discovered to play a role in instigating the hyphal formation and virulence in C. albicans.

Candidalysin

Candidalysin is a cytolytic 31-amino acid α-helical peptide toxin that is released during hyphal formation. It contributes to virulence during mucosal infections.

Epidemiology

Candida is found worldwide but most commonly compromises immunocompromised individuals diagnosed with serious diseases such as HIV and cancer. Candida are ranked as one of the most common groups of organisms that cause nosocomial infections. Especially high risk individuals are patients in Intensive Care Units (ICU), have recently undergone surgery or transplant. Candida albicans infections is the top source of fungal infections in critically ill or otherwise immuncompromised patients. These patients predominantly develop oropharyngeal or thrush candidiasis, which can lead to malnutrition and interfere with the absorption of medication. Parts of the body that are commonly infected include the skin, genitals, throat, mouth, and blood. Candida continues to be the fourth most commonly isolated organism in bloodstream infections (BSIs). Furthermore, Candida albicans bloodstream infections have been associated with a high mortality rate. Methods of transmission include mother to infant through childbirth, people-to-people acquired infections that most commonly occur in hospital settings where immunocompromised patients acquire the yeast from healthcare workers and has a 40% incident rate. Men can become infected after having sex with a woman that has an existing vaginal yeast infection. Although Candida albicans is the most common cause of candidemia, there has been a decrease in the incidence and an increases isolation of non-albicans species of Candida in recent years. Preventive measures include keeping a healthy lifestyle including good nutrition, proper nutrition, and careful antibiotic use.

Application in engineering

Candida albicans has been used in combination with carbon nanotubes (CNT) to produce stable electrically conductive bio-nano-composite tissue materials that have been used as temperature sensing elements

Treatment

Treatment commonly includes: