Heterozygosis and Pathogenicity of Cryptococcusneoformans AD-Hybrid Isolates
Nineteen Cryptococcusneoformans AD-hybrid isolates were investigated to assess whether hybrid genomic background could affect virulence in a mouse model. The level of heterozygosity of each strain was analyzed using primers specific for allele A and D of 15 polymorphic genes. Virulence was tested in a mouse model of systemic infection by measuring time of survival. In addition, the putative virulence attributes, melanin, phospholipase, and capsule production, as well as growth at 39°C and UV sensitivity were investigated. Eight strains showed to be heterozygous in up to 70% of loci, other eight strains were heterozygous in less than 60% of loci, while the remaining three strains were homozygous at all tested loci. Mice infected with hybrids with a high percentage of heterozygosis showed significantly (P < 0.01) shorter survival than mice infected with the other hybrids. Mortality was not correlated with the mating-type locus pattern, as well as it was not correlated with the level of expression of the different virulence attributes investigated. The present study confirms that hybridization in C. neoformans could represent an important evolutionary driving force in increasing the fitness of this yeast in the environment and in the host.
KeywordsCryptococcusneoformans AD hybrids Heterozygosis Virulence factors Mating type
- 1.Heitman J, Kozel R, Kwon-Chung KJ, Perfect JR, Casadevall A. Cryptococcus. From human pathogen to model yeast. Washington, DC: ASM Press; 2011.Google Scholar
- 13.Viviani MA, Antinori S, Cogliati M, Esposto MC, Pinsi G, Casari S, et al. European Confederation of Medical Mycology (ECMM) prospective survey of cryptococcosis: report from Italy. Med Mycol. 2002;40:507–17.Google Scholar
- 25.Price MF, Wilkinson ID, Gentry LO. Plate method for detection of phospholipase activity in Candida albicans. 1982:7–14.Google Scholar
- 28.Sun S, Xu J. Chromosomal rearrangements between serotype A and D in Cryptococcus neoformans. PlosOne. 2009;4:1–17.Google Scholar
- 29.Li W, Ni M, Averette AF, Desnos-Ollivier M, Dromer F, Heitman J. Genetic diversity and genomic plasticity of Cryptococccus neoformans AD hybrids. In: 8th international conference on Cryptococcus and Cryptococcosis, 1–5 May 2011, Charleston, SC, USA. Poster 15.Google Scholar