Just
sharing the information that I have taken from the Weikipedia and other
resource… hope it will be useful for all of us.. Never take everything
slightly.
Candida
albicans is a diploid fungus that grows both as yeast and filamentous cells and
a causal agent of opportunistic oral and genital infections in humans. Systemic
fungal infections (fungemias) including those by C. albicans have emerged as
important causes of morbidity and mortality in immunocompromised patients
(e.g., AIDS, cancer chemotherapy, organ or bone marrow transplantation). C.
albicans biofilms may form on the surface of implantable medical devices. In
addition, hospital-acquired infections by C. albicans have become a cause of
major health concerns.
C.
albicans is commensal and a constituent of the normal gut flora comprising
microorganisms that live in the human mouth and gastrointestinal tract. C.
albicans lives in 80% of the human population without causing harmful effects,
although overgrowth of the fungus results in candidiasis (candidosis).
Candidiasis is often observed in immunocompromised individuals such as
HIV-infected patients. A common form of candidiasis restricted to the mucosal
membranes in mouth or vagina is thrush, which is usually easily cured in people
who are not immunocompromised. For example, higher prevalence of colonization
of C. albicans was reported in young individuals with tongue piercing, in
comparison to non-tongue-pierced matched individuals. To infect host tissue, the usual unicellular
yeast-like form of C. albicans reacts to environmental cues and switches into
an invasive, multicellular filamentous form, a phenomenon called dimorphism.
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, chromosomedeletions 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.
The C.
albicans genome for strain SC5314 was sequenced at
the Stanford
DNA Sequencing and Technology Center. The genome of the WO1 strain was
sequenced by the Broad Institute of MIT and Harvard.
The
sequencing of the C. albicans genome and subsequently of the
genomes of several other medically relevant Candida species
has profoundly and irreversibly changed the way Candida species
are now investigated and understood. The C. albicans genome
sequencing effort was launched in October 1996. Successive releases of the
sequencing data and genome assemblies have occurred in the last 10 years,
culminating in the release of the diploid assembly 19, which provided a haploid
version of the genome along with data on allelic regions in the genome. A
refined assembly 20 with the eight assembled C. albicans chromosomes
was released in the summer of 2006. Importantly, the availability of sequencing
data prior to the completion of the genome sequence has made it possible to
start C. albicans post-genomics early on. In this regard,
genome databases have been made available to the research community providing
different forms of genome annotation. These have been merged in a
community-based annotation hosted by the CandidaGenome Database. The
availability of the genome sequence has paved the way for the implementation of
post-genomic approaches to the study of C. albicans: macroarrays
and then microarrays have been developed and used to study
the C. albicans transcriptome;
proteomics has also been developed and complements transcriptional analyses;
furthermore, systematic approaches are becoming available to study the
contribution of each C. albicans gene in different contexts.
Other Candida genome sequences have been, or are being,
determined: C. glabrata, C. dubliniensis, C.
parapsilosis, C. guilliermondii, C. lusitaniae, and C. tropicalis. These species will soon enter
the post-genomic era as well and provide interesting comparative data. The
genome sequences obtained for the different Candida species
along with those of non-pathogenic hemiascomycetes provide
a wealth of knowledge on the evolutionary processes that shaped the
hemiascomycete group, as well as those that may have contributed to the success
of different Candida species as pathogens. 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 universal genetic code (most such
departures are in start codons or, for eukaryotes, mitochondrial genetic codes). This alteration may
help these Candida species (in some environments) 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 of C.
albicans and population studies in this species. The genome sequence
has allowed for identifying the presence of a parasexual cycle (no meiotic division)
in C. albicans. This parasexual cycle is under the control of mating-type loci and
switching between white and opaque phenotypes. Investigating the role the
mating process plays in the dynamics of the C. albicans population
or in other aspects of C. albicans biology and pathogenicity
will undoubtedly represent an important focus for future research. A
similar lack of meiosis was found in Saccharomyces cerevisiae altered
to use the same genetic code as C. albicans.
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. The
ability of C. albicans to form hyphae has been proposed as a virulence factor,
as these structures are often observed invading tissue, and C. albicans strains
that are unable to form hyphae are defective in causing infection.
Round
white-phase and elongated opaque-phase Candida albicans cells. Scale bar is 5
µm.
Model
of the genetic network regulating the white-opaque switch. White and gold boxes
represent genes enriched in the white and opaque states, respectively. The Blue
lines represent relationships based on genetic epistasis. Red lines represent
Wor1 control of each gene, based on Wor1 enrichment in chromatin
immunoprecipitation experiments. Activation (arrowhead) and repression (bar)
are inferred based on white- and opaque-state expression of each gene.
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
areexpressed differently in different colony
morphologies have been identified, some recent efforts focus on what might
control these changes. Further, whether there is a potential molecular link
between dimorphism and phenotypic switching 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 that 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 say that 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.
The heterozygosity of
the Candida genome exceeds that found in other genomes and is
widespread among clinical isolates. Non-synonymous 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.
Treatment
- amphotericin
B, caspofungin, or fluconazole for
systemic infections
- fluconazole
or caspofungin for oral or esophageal infections
- topical azole for
vaginal infections
So.. guys beware of it yea… healthy lifestyle lead to
healthy and happy life.. J
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