Congenic strains for genetic analysis of virulence traits in Cryptococcus gattii

Infect Immun. 2013 Jul;81(7):2616-25. doi: 10.1128/IAI.00018-13. Epub 2013 May 13.

Abstract

Cryptococcus gattii is responsible for a large outbreak of potentially fatal disease that started in the late 1990s on Vancouver Island, Canada. How this fungus and the outbreak isolates in particular cause disease in immunocompetent people is unknown, with differing hypotheses. To explore genetic contributions, a pair of congenic a and α mating type strains was generated by a series of 11 backcrosses to introgress the MAT locus from a nonoutbreak strain into the background of strain R265, isolated from a Vancouver Island patient. The congenic pair was used to investigate three traits: mitochondrial inheritance, the effect of the MAT alleles on virulence, and the impact of a predicted virulence factor on pathogenicity. The two congenic strains show the same virulence in different models of cryptococcosis and equivalent levels of competition in coinfection assays. These results rule out a role of the MAT locus and mitochondrial genotype as major virulence factors in the outbreak strains. Disruption of Bwc2, a light-dependent transcription factor, resulted in reduced virulence, consistent with a similar function in the related species Cryptococcus neoformans. The C. gattii congenic strains represent a new resource for exploring the evolution of virulence in the C. neoformans-C. gattii clade.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism
  • Coculture Techniques
  • Coinfection
  • Cryptococcosis / microbiology*
  • Cryptococcus gattii / genetics*
  • Cryptococcus gattii / metabolism
  • Cryptococcus gattii / pathogenicity
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / metabolism
  • Cryptococcus neoformans / pathogenicity
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genes, Fungal*
  • Genetic Complementation Test
  • Genetic Loci
  • Genetic Markers
  • Genetic Variation
  • Humans
  • Inheritance Patterns
  • Mice
  • Mice, Inbred A
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Recombination, Genetic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Virulence

Substances

  • Fungal Proteins
  • Genetic Markers
  • Transcription Factors