title: Cryptococcus neoformans with a mutation in the tetratricopeptide repeat-containing gene, CCN1, causes subcutaneous lesions but fails to cause systemic infection.
abstract: 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.
authors.affiliation: Molecular Microbiology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Seyung
authors.initials: S
authors.lastname: Chung
authors.forename: Philippe
authors.initials: P
authors.lastname: Mondon
authors.forename: Yun C
authors.initials: YC
authors.lastname: Chang
authors.forename: Kyung J
authors.initials: KJ
authors.lastname: Kwon-Chung
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002371:Cat Diseases / Q000382:microbiology / Q000473:pathology; D002415:Cats; D003453:Cryptococcosis / Q000382:microbiology / Q000473:pathology / Q000662:veterinary; D003455:Cryptococcus neoformans / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D003881:Dermatomycoses / Q000382:microbiology / Q000473:pathology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006099:Granuloma / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009296:Nasal Cavity / Q000382:microbiology / Q000473:pathology; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics*; D013696:Temperature; D014774:Virulence
chemical_list: C473780:CCN1 protein, Cryptococcus neoformans; D005656:Fungal Proteins