Candida albicans

Candida albicans is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usually a commensal organism, but it can become pathogenic in immunocompromised individuals under a variety of conditions. It is one of the few species of the genus Candida that cause the human infection candidiasis, which results from an overgrowth of the fungus. Candidiasis is, for example, often observed in HIV-infected patients.
C. albicans is the most common fungal species isolated from biofilms either formed on implanted medical devices or on human tissue. C. albicans, C. tropicalis, C. parapsilosis, and C. glabrata are together responsible for 50–90% of all cases of candidiasis in humans. A mortality rate of 40% has been reported for patients with systemic candidiasis due to C. albicans. By one estimate, invasive candidiasis contracted in a hospital causes 2,800 to 11,200 deaths yearly in the US.
C. albicans is commonly used as a model organism for fungal pathogens. It is generally referred to as a dimorphic fungus since it grows both as yeast and filamentous cells. However, it has several different [|morphological] phenotypes including opaque, GUT, and pseudohyphal forms. C. albicans was for a long time considered an obligate diploid organism without a haploid stage. This is, however, not the case. Next to a haploid stage C. albicans can also exist in a tetraploid stage. The latter is formed when diploid C. albicans cells mate when they are in the opaque form. The diploid genome size is approximately 29 Mb, and up to 70% of the protein coding genes have not yet been characterized.
C. albicans is easily cultured in the lab and can be studied both in vivo and in vitro. Depending on the media different studies can be done as the media influences the morphological state of C. albicans. A special type of medium is CHROMagar Candida, which can be used to identify different Candida species.

Etymology

"Candida albicans" can be read as tautological. "Candida" comes from the Latin word "candidus", meaning "shining white". "Albicans" itself is the present participle of the Latin word "albicō", meaning "becoming white". This leads to one possible interpretation as the redundant phrase "pure white becoming white".
It is often shortly referred to as thrush, candidiasis, or candida.
More than a hundred synonyms have been used to describe C. albicans.
Over 200 species have been described within the candida genus. The oldest reference to thrush, most likely caused by C. albicans, dates back to 400 BC in Hippocrates' work Of the Epidemics describing oral candidiasis.

Genome

The genome of C. albicans is almost 16Mb for the haploid size and consists of 8 sets of chromosome pairs called chr1A, chr2A, chr3A, chr4A, chr5A, chr6A, chr7A and. The second set has similar names but with a B at the end. Chr1B, chr2B,... and chrRB. The whole genome contains 6,198 open reading frames. Seventy percent of these ORFs have not yet been characterized. The whole genome has been sequenced making it one of the first fungi to be completely sequenced. All open reading frames are also available in Gateway-adapted vectors. Next to this ORFeome there is also the availability of a GRACE library to study essential genes in the genome of C. albicans. The most commonly used strains to study C. albicans are the WO-1 and SC5314 strains. The WO-1 strain is known to switch between white-opaque form with higher frequency while the SC5314 strain is the strain used for gene sequence reference.
One of the most important features of the C. albicans genome is the high heterozygosity. At the base of this heterozygosity lies the occurrence of numeric and structural chromosomal rearrangements and changes as means of generating genetic diversity by chromosome length polymorphisms, reciprocal translocations, chromosome deletions, Nonsynonymous single-nucleotide polymorphisms and trisomy of individual chromosomes. These karyotypic alterations lead to changes in the phenotype, which is an adaptation strategy of this fungus. These mechanisms are further being explored with the availability of the complete analysis of the C. albicans genome.
An unusual feature of the genus Candida is that in many of its species 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. However, this different codon usage makes it more difficult to study C. albicans protein-protein interactions in the model organism S. cerevisiae. To overcome this problem a C. albicans specific two-hybrid system was developed.
The genome of C. albicans is highly dynamic, contributed by the different CUG translation, 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 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 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.

Morphology

C. albicans exhibits a wide range of morphological phenotypes due to phenotypic switching and bud to hypha transition. The yeast-to-hyphae transition 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. Other systems have been described as well. Two systems 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. 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. 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 are generated spontaneously. This type of switching does not occur en masse, represents a variability system and it happens independently from environmental conditions. The strain 3153A produces at least seven different colony morphologies. In many strains the different phases convert spontaneously to the other 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 phenotypes makes C. albicans able to grow in different environments, both as a commensal and as a pathogen.
In the 3153A strain, a gene called SIR2, which seems to be important for phenotypic switching, has been found. SIR2 was originally found in Saccharomyces cerevisiae, 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. 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.