Candida albicans

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Microscopic image of Candida Albicans.
See also: Candidiasis

Candida albicans is a fungus, able to sexually reproduce. It is a common occupant of the human intestine. It is often associated with yeast related diseases, candidiasis, in the genitals and in the mouth of animals. It is one of the most common pathogens found in humans and is the source of a variety of different infections.

Like most microorganisms found in the digestive tract of animals, C. albicans falls into a class of relationships that occur between organisms where one benefits and the other is not significantly harmed or benefited. C. albicans can be found in most of the general population causing no detrimental side effects. Although it is not found to be harmful, an overgrowth of C. albicans, known as candidasis, is harmful to the individual. Individuals with a healthy immune system are able to fight off the disease, however in HIV patients with weakened immune systems; it is much more difficult for the disease to be fought off and can lead to more serious problems. In order for the disease to be transmitted to the host, the yeast form of C. albicans responds to changes in the environment, becomes harmful, and changes from a unicellular form into a multicellular.

Cell Structure and Metabolism

The exterior of the Candida albicans cell is made up of many types of polysaccharides such as, glucan, chitin, and mannan. The first two mainly give structure to the cell, while the latter, mannan, a protein, makes up the main antigen of the organism. The cellular structure of C. albicans has recently been considered a dynamic organelle. Mannoproteins have acidic activity and ligand-receptor functions. Fibrinogen, and many extra-cellular matrix components are among the host proteins held in place by cell wall proteins.[1] The receptors of C. albicans are mannoproteins that are needed for the adherence of the organism to the endothelial cells. This is specifically the case for the CR-3 protein of C. albicans. It was discovered that CR3 was the receptor for endothelial cells because mutants without CR3 activity were less adherent and less virulent in vitro. Additionally, the ligand recognized by the CR3 receptor, blocked adherence of the organism to the endothelial cells. Surface mannoproteins are tough immunogens that activate and change the host immune response during candidiasis.

The CR2 of C. albicans promotes the adherence of the organism to the plastic substrates. Contrasting the CR2 of mammalian cells, the Candida CR2 identifies ligands containing the RGD sequence of amino acids. A mannoprotein has also been found to be the cause of adhesion for epithelial cells. The mannoproteins of C.albicans are thought to possibly be growth phase and growth from specific. Like many fungi, Candida albicans displays morphological plasticity, this characteristic can be related to its biological ability to act as an opportunistic pathogen to humans. Modifications in cell shape require incorporation of many cellular functions, and take place in response to environmental changes, most commonly pH and temperature.

Genome

C. albicans was one of the first eukaryotic pathogens chosen for gene sequencing. The genome of Candida albicans was sequenced due to the fact that it is one of the most common human fungal pathogen. Most isolates of C. albicans used for genetic analysis are mostly diploid and some even contain translocations in their genes. Unlike most species that undergo sequencing, a haploid form of C. albicans is unavailable. Due to its extensive use in molecular analyses and virulence in animal models, SC5314(7) was selected for large- scale sequencing. C. albicans was first sequenced at the Stanford DNA Sequencing and Technology Center. The diploid sequence assembly displayed the amount of heterozygosity in the strain SC5314. The results obtained from this along with results from the sequencing afforded many important discoveries in C. albicans development.[2]

To put together the C. albicans diploid genome sequence, a commonly used assembly program called the “phrap” was used. Using the phrap, resulted in an assembly in which the products of the overlapping DNA fragments (contigs), were as much as 20% much greater than the size of the haploid genome.The ultimate diploid sequence was disperesed over 412 supercontigs, 146 homologous pairs, 119 phrap contigs, and one supercontig produced from two phrap contigs joined on the basis of GenBank sequence.The genome sequence shows many adaptations that are needed for environmental responding and sensing. Due to the fact that C. albicans is able to pass through the digestive tract, it requires it to be able to deal with extreme variations of pH. A number of genes associated with pH regulatory have been found in C. albicans.

Heterozygosity

Clinical isolate of Candida albicans.

The heterozygosity (the genetic variation in a population) of the Candida genome surpasses most microbes in other genomes and is commonly found in clinical isolates. The diploid assembly clearly shows the extent amount of heterozygosity in C. albicans. The entire population of C. albicans is said to have high polymorphisms. The average frequency of polymorphism is one in 237 bases. Many allelic differences have been found in C. albicans but their significance is not known. It is thought that these differences may increase genetic diversity and add to the development of drug resistance.[3]

The polymorphisms found in C. albicans are distributed unevenly across its genome. Dissimilar single base polymorphisms yield two proteins that have differences in one or many amino acids that may give functional differences for each protein. This circumstance increases the amount of different types of proteins determined by the genome.

Current research

"Candida albicans and inflammatory bowel disease"

It has been recently discovered that Candida albicans syndrome impinges upon one third of the U.S. population. The illness takes its form in many variations affecting the lymphatic, digestive, reproductive, and urinary systems. The fungus known as Candida albicans can be seen in most healthy individuals, however when an immune system can not protect itself fully, this bacteria multiplies and rapidly overproduces itself. This overproduction release toxins that are then absorbed into the bloodstream, and can cause and individual to get a variety of unpleasant ailments. It has recently been discovered that AIDS patients and cancer patients with this “ailment” have many complications due to their weakened immune system and their inability to fight it off. An additional complication Candidas albicans raises is infertility in males and females.The yeast colonies formed survive by consuming dead tissue. It only becomes a health threat when something impacts the growth and overproduction of the colonies. This can occur for many reasons such as, antibiotics, birth control pills, and artificial hormones. When these are introduced, other bacteria are “killed off” in turn giving more room for the yeast colonies to grow.

The overgrowth of Candida can become visible in many different ways such as, allergic reactions, and gastrointestinal and urinary tract disorders. Given that Candida albicans can be found over must of the body even in healthy individuals, testing for it in a laboratory will not help much. The way to measure if it is malignant or not is to test the amount of antigens found in an individuals blood serum which in turn corresponds to the amount of yeast.[4]

"Candida Albicans Genome Fully Annotated: The National Research Council of Canada heads an international team, bringing new hope to people with immune system deficiencies"

The National Research Council Biotechnology Research Institute announced the publication of an article that discloses the complete genomic explanation of Candida albicans. C. Albicans is a fungal pathogen and is one of the most common causes of infection in people that are immunocompromised, and is currently becoming more complicated to treat. It is a single cell fungus exists naturally in normal human bacterial contents. Around 30 to 40% of serious fungal infections that are mostly attributable to C. Albicans, result in death. Individuals most vulnerable to this yeast are premature infants, transplant recipients taking immunosuppressive drugs, HIV positive patients, and cancer patients.

Candida is the leading fungal infection in hospitals today. The treatments currently given are only effective to an extent due to the microorganism’s resistance to antibiotics. The complete and accurate annotation of Candidas genome, will aid researchers in better understanding the pathogens weaknesses and improve existing therapeutic agents. Based on C. albicans annotations, researchers have been able to produce the first non- commercial microarray that can be used by researchers globally to study the genomic and polemics of Candida. The microarray of Candida is made up of an arrangement of around 600 DNA samples on a single glass slide. There are others that differ in size and are used to examine entire genomes. They are able to concurrently evaluate the expression and interactions of an organism’s gene, which is an important factor in developing more effective medical treatments.

"A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation."

Fungal infections have become a universal problem among severely immunocompromised patients, especially in those who undergo bone marrow transplantation. A double- blind experiment what conducted in which patients receiving bone marrow transplants were randomly assign to receive two different conditions; one being a placebo and the other being the drug fluconazole (400 mg. daily). Both conditions were administered prophylactically from the beginning of the study up until the patients neutrophil count returned to 1000 per mL, toxicity was found, or if a fungal infection was suspected. At the conclusion of the treatment, 67% of the 177 patients who were placed in the placebo condition had a positive fungal culture, compared to the 29.6% of the 179 patients who were receiving fluconazole. Fungal infections were found in 28 patients who received placebo compared to 5 patients who received fluconazole. It was found that fluconazole prevented infections with all strains of Candida except for one. Fluconazole had no ill side effects besides for increasing alanine amino transference levels in patients who received it. There was no major difference in overall mortality between both conditions, however fewer deaths were attributed to systemic fungal infections in the patients who were given fluconazole, opposed to those receiving the placebo (1 of 179 vs. 10 of 177). The results concluded that careful administration of fluconazole given to patients undergoing bone marrow transplants, reduced the occurrence of system fungal infections.<ref<Collins, C. D., Ellis, J. J., Kaul, D. R. (2008). Comparative cost-effectiveness of posaconazole versus fluconazole or itraconazole prophylaxis in patients with prolonged neutropenia. Am J Health Syst Pharm 65: 2237-2243.</ref>

References

  1. Chaffin, W. L. (2008). Candida albicans Cell Wall Proteins. Microbiol. Mol. Biol. Rev. 72: 495-544.
  2. Chibana, H., Magee, B. B., Grindle, S., Ran, Y., Scherer, S. & Magee, P. T. (1998) Genetics 149 , 1739-1752.
  3. Jones T, Federspiel NA, Chibana H, et al (May 2004). "The diploid genome sequence of Candida albicans". Proceedings of the National Academy of Sciences 101 (19): 7329–34.
  4. Pierce, C. G., Thomas, D. P., Lopez-Ribot, J. L. (2009). Effect of tunicamycin on Candida albicans biofilm formation and maintenance. J Antimicrob Chemother 63: 473-479.