Cryptococcus neoformans with a mutation in the tetratricopeptide repeat-containing gene, CCN1, causes subcutaneous lesions but fails to cause systemic infection

Infect Immun. 2003 Apr;71(4):1988-94. doi: 10.1128/IAI.71.4.1988-1994.2003.


We studied a Cryptococcus neoformans strain that caused feline chronic nasal granuloma without disseminated disease. This strain, B-4551, grows at temperatures up to 35 degrees C and fails to cause systemic infection in mice. Many cells of B-4551 formed short hyphal elements in feline nasal tissue and occasionally at 35 degrees C in vitro. A complementation and sequence analysis revealed that the temperature-sensitive (Ts) phenotype of B-4551 was due to deletion of a lysine residue in the cryptococcal CCN1 gene. B-4551 complemented with the wild type CCN1 gene grew at 37 degrees C and caused fatal systemic infection in mice. The CCN1 gene encodes a protein containing 16 copies of a tetratricopeptide repeat. CCN1 is homologous to the Saccharomyces cerevisiae CLF1 gene, which is required for pre-mRNA splicing, cell cycle progression, and DNA replication, and to the Drosophila melanogaster crn gene, which is involved in neurogenesis. CLF1 complemented the Ts phenotype of B-4551. CCN1, however, failed to rescue the clf1 mutant in S. cerevisiae. These results indicate that the Ccn1p may not be as functionally diverse as Clf1p in yeast.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cat Diseases / microbiology
  • Cat Diseases / pathology
  • Cats
  • Cryptococcosis / microbiology
  • Cryptococcosis / pathology
  • Cryptococcosis / veterinary
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / growth & development
  • Cryptococcus neoformans / pathogenicity*
  • Dermatomycoses / microbiology
  • Dermatomycoses / pathology
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Granuloma / microbiology
  • Granuloma / pathology
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Nasal Cavity / microbiology
  • Nasal Cavity / pathology
  • Repetitive Sequences, Amino Acid / genetics*
  • Temperature
  • Virulence


  • CCN1 protein, Cryptococcus neoformans
  • Fungal Proteins

Associated data

  • GENBANK/AF265234