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Loss of Heterozygosity in the Diploid Fungal Pathogen Candida Albicans is Associated with Changes in Resistance and Virulence Traits

Doha Abdullah and Dr. Robert Akins, Department of Biochemistry, Immunology and Microbiology, Wayne State University School of Medicine, 550 E Canfield, Detroit MI 48201.

C. albicans is the most successful human fungal pathogen causing vaginal candidiasis in 40% of American women, oral lesions, and 25,000 cases of candidemia in the USA with an estimated mortality rate of 20%. The central question of my proposal is whether antifungal stress, which induces loss of heterozygosity (LOH) mutations in this diploid yeast, concurrently induces phenotypic changes associated with virulence. I found among a set of 41 flucytosine-stressed and 40 control isolates that the percent of stressed isolates with LOH is 17 fold greater, resistance to terbinafine, rotenone, and cyanide-salicylhydroxamic acid was 26-, 23- and 51-fold greater, invasiveness was 20 fold greater, and biofilm formation was 2 times more than seen in controls. Additionally, Invasiveness prevalence did not diminish after subculturing the isolates collection. Epigenetic changes should disappear after subculturing, whereas LOH induced changes are mutational and should be stable.These data indicate that LOH is associated with phenotypic changes seen in a high percent of stressed cells. Additional molecular characterization of LOH by whole genome sequencing could map the subset of alterations that confer these phenotypic changes. LOH may be an important pathway in the adaptive responses of C. albicans to antifungals and to the host. Verifying that is a first step in understanding the pathway and in identifying new targets for antifungal intervention.

 

 




Additional Abstract Information

Presenter: Doha Abdullah

Institution: Wayne State University

Type: Oral

Subject: Microbiology

Status: Approved


Time and Location

Session: Oral 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 235
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