The object of the research is to devise a method of genetic analysis for Candida albicans. Previous work has shown that the cells are diploid, that many natural isolates contain recessive auxotrophic mutations, and that these mutations can be exposed by UV- and nitrous acid-induced mitotic crossing over. Spheroplast fusion can also be used to construct novel phenotypes and identify alleles. We will continue our mapping and complementation studies using mitotic crossing-over and spheroplast fusion. We will also use a C. albicans clone bank to devise a transformation system, based on the techniques used in Saccharomyces. The clone bank has been constructed in the chimeric E. coli-S. cerevisiae vector YEp13 and consists of 4463 colonies, each containing about 7.5 kb of Canadida DNA. We will use this bank to look for C. albicans sequences which complement S. cerevisiae nutritional deficiencies and for C. albicans sequences which complement C. albicans auxotrophies. We will also try to use known S. cerevisiae genes( ARG4, TRP1, TRP5, H1S3) to complement C. albicans deficiencies. We will isolate mutants in properties of C. albicans thought to be associated with virulence and test the mutants for their virulence in mice. These studies will further our knowledge of the genetic basis of virulence in this important human pathogen and may serve as a model system for parasexual analysis of other pathogens which are presently recalcitrant to genetic investigations.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Genetics Study Section (GEN)
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Michigan State University
Schools of Arts and Sciences
East Lansing
United States
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Chibana, Hiroji; Magee, Paul T (2009) The enigma of the major repeat sequence of Candida albicans. Future Microbiol 4:171-9
Magee, B B; Sanchez, Melissa D; Saunders, David et al. (2008) Extensive chromosome rearrangements distinguish the karyotype of the hypovirulent species Candida dubliniensis from the virulent Candida albicans. Fungal Genet Biol 45:338-50
van het Hoog, Marco; Rast, Timothy J; Martchenko, Mikhail et al. (2007) Assembly of the Candida albicans genome into sixteen supercontigs aligned on the eight chromosomes. Genome Biol 8:R52
Lephart, Paul R; Magee, Paul T (2006) Effect of the major repeat sequence on mitotic recombination in Candida albicans. Genetics 174:1737-44
Ibrahim, Ashraf S; Magee, B B; Sheppard, D C et al. (2005) Effects of ploidy and mating type on virulence of Candida albicans. Infect Immun 73:7366-74
Lephart, Paul R; Chibana, Hiroji; Magee, Paul T (2005) Effect of the major repeat sequence on chromosome loss in Candida albicans. Eukaryot Cell 4:733-41
Jones, Ted; Federspiel, Nancy A; Chibana, Hiroji et al. (2004) The diploid genome sequence of Candida albicans. Proc Natl Acad Sci U S A 101:7329-34
Cassola, Alejandro; Parrot, Marc; Silberstein, Susana et al. (2004) Candida albicans lacking the gene encoding the regulatory subunit of protein kinase A displays a defect in hyphal formation and an altered localization of the catalytic subunit. Eukaryot Cell 3:190-9
Legrand, Melanie; Lephart, Paul; Forche, Anja et al. (2004) Homozygosity at the MTL locus in clinical strains of Candida albicans: karyotypic rearrangements and tetraploid formation. Mol Microbiol 52:1451-62
Iwaguchi, Shin-Ichi; Suzuki, Mina; Sakai, Naomi et al. (2004) Chromosome translocation induced by the insertion of the URA blaster into the major repeat sequence (MRS) in Candida albicans. Yeast 21:619-34

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