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Infection and Immunity, July 2008, p. 2923-2938, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00168-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans ^,

Xiaorong Lin, Kirsten Nielsen, Sweta Patel, and Joseph Heitman^*

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina

Received 7 February 2008/ Returned for modification 8 March 2008/ Accepted 7 April 2008

Hybridization with polyploidization is a significant biological force driving evolution. The effect of combining two distinct genomes in one organism on the virulence potential of pathogenic fungi is not clear. Cryptococcus neoformans, the most common cause of fungal infection of the central nervous system, has a bipolar mating system with a and mating types and occurs as A (haploid), D (haploid), and AD hybrid (mostly diploid) serotypes. Diploid AD hybrids are derived either from a- mating or from unisexual mating between haploid cells. The precise contributions of increased ploidy, the effect of hybridization between serotypes A and D, and the combination of mating types to the virulence potential of AD hybrids have remained elusive. By using in vitro and in vivo characterization of laboratory-constructed isogenic diploids and AD hybrids with all possible mating type combinations in defined genetic backgrounds, we found that higher ploidy has a minor negative effect on virulence in a murine inhalation model of cryptococcosis. The presence of both mating types a and in AD hybrids did not affect the virulence potential, irrespective of the serotype origin. Interestingly, AD hybrids with only one mating type behaved differently, with the virulence of AD strains similar to that of other hybrids, while aADa hybrids displayed significantly lower virulence due to negative epistatic interactions between the Aa and Da alleles of the mating type locus. This study provides insights into the impact of ploidy, mating type, and serotype on virulence and the impact of hybridization on the fitness and virulence of a eukaryotic microbial pathogen.

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* Corresponding author. Mailing address: Room 322 CARL Building, Box 3546 Research Drive, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu

Published ahead of print on 21 April 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Casadevall

Present address: Department of Biology, Texas A & M University, College Station, TX.

Present address: Department of Microbiology, University of Minnesota, Minneapolis, MN.

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Infection and Immunity, July 2008, p. 2923-2938, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00168-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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