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Originally published as Genetics Published Articles Ahead of Print on June 18, 2005.

Genetics, Vol. 171, 975-983, November 2005, Copyright © 2005
doi:10.1534/genetics.105.045039

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Interaction Between Genetic Background and the Mating-Type Locus in Cryptococcus neoformans Virulence Potential

Kirsten Nielsen*,{dagger}, Robert E. Marra*,1, Ferry Hagen{ddagger}, Teun Boekhout{ddagger},§, Thomas G. Mitchell*, Gary M. Cox** and Joseph Heitman*,{dagger},**,{dagger}{dagger},2

* Department of Molecular Genetics and Microbiology, ** Department of Medicine and {dagger}{dagger} Department of Pharmacology and Cancer Biology, {dagger} Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710 and {ddagger} Department of Comparative Genomics and Bioinformatics, Centraalbureau voor Schimmelcultures and § Department of Internal Medicine and Infectious Diseases, University Medical Center, 83584 Utrecht, The Netherlands

2 Corresponding author: Department of Molecular Genetics and Microbiology, 322 CARL Bldg., Research Dr., Duke University Medical Center, Durham, NC 27710.
E-mail: heitm001{at}duke.edu

The study of quantitative traits provides a window on the interactions between multiple unlinked genetic loci. The interaction between hosts and pathogenic microbes, such as fungi, involves aspects of quantitative genetics for both partners in this dynamic equilibrium. One important pathogenic fungus is Cryptococcus neoformans, a basidiomycete yeast that can infect the human brain and whose mating system has two mating type alleles, a and {alpha}. The {alpha} mating-type allele has previously been linked to increased virulence potential. Here congenic C. neoformans strains were generated in the two well-characterized genetic backgrounds B3501{alpha} and NIH433a to examine the potential influence of genes outside of the mating-type locus on the virulence potential of mating type. The congenic nature of these new strain pairs was established by karyotyping, amplified fragment length polymorphism genotyping, and whole-genome molecular allele mapping (congenicity mapping). Virulence studies revealed that virulence was equivalent between the B3501 a and {alpha} congenic strains but the {alpha} strain was more virulent than its a counterpart in the NIH433 genetic background. These results demonstrate that genomic regions outside the mating type locus contribute to differences in virulence between a and {alpha} cells. The congenic strains described here provide a foundation upon which to elucidate at genetic and molecular levels how mating-type and other unlinked loci interact to enable microbial pathogenesis.




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