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Mating type Zygosity and Virulence in a Human Pathogenic Fungus Candida Albicans

7 View(s), published at 2007, written by Wei Wu, published by ProQuest
Mating type Zygosity and Virulence in a Human Pathogenic Fungus Candida Albicans

Mating-type zygosity and virulence in a human pathogenic fungus, candida albicans by Wei Wu Candida albicans is an obligate diploid fungal pathogen of humans, and neither a complete sexual life cycle nor meiosis has been described. The majority of natural C. albicans strains is heterozygous .... Published date on: 2007 with total page: 183 pages. Publisher of Mating-type Zygosity and Virulence in a Human Pathogenic Fungus, Candida Albicans is ProQuest.

Candida albicans is an obligate diploid fungal pathogen of humans, and neither a complete sexual life cycle nor meiosis has been described. The majority of natural C. albicans strains is heterozygous (a/alpha) at the mating type locus (MTL), and must undergo MTL-homozygosis to mate. The research described in this thesis focuses on the mechanisms of MTL-homozygosis and the role of the MTL locus in virulence and pathogenesis. To understand how MTL-homozygosity was achieved, polymorphic markers on chromosome 5 were analyzed in the spontaneously derived and natural MTL-homozgyous strains. It is demonstrated that chromosome loss followed by duplication of the retained homolog (uniparental disomy) is the most common mechanism in the spontaneous generation of MTL-homozygotes in vitro, whereas natural MTL-homozygous strains undergo mitotic recombination to achieve MTL-homozygosis. To understand how the mating type locus contributes to virulence, a murine model for systemic infection was employed to compare the virulence of strains that differ in zygosity of the MTL locus and genes on chromosome 5. Natural a/alpha strains of C. albicans are more virulent and more competitive than their spontaneous MTL -homozygous offspring. Deletion of either the a or alpha copy of the MTL locus of natural a/alpha strains results in a small decrease in virulence, and a small decrease in competitiveness. Loss of heterozygosity of non-MTL genes along chromosome 5, however, results in larger decreases in virulence and competitiveness. Natural MTL-homozygous strains are on average less virulent than natural MTL-heterozygous strains and arise by multiple mitotic recombinations along chromosome 5 outside of the MTL region. These results are consistent with the hypothesis that a competitive advantage of natural a/alpha strains over MTL-homozygous offspring maintains the mating system of C. albicans.

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