Cryptococcus neoformans is a pathogenic yeast which belongs to Basidiomycetes, a taxonomic Class phylogenetically remote from the rest of the pathogenic yeasts (Ascomycetes). C. neoformans causes fatal meningoencephalitis primarily in patients with T- lymphocyte dysfunction and is the only species in the genus Cryptococcus that has optimum growth at temperatures higher than 30C. Although extensive studies on the molecular bases of cell cycle and morphogenesis have been carried out in ascomycetous yeasts, such studies have not been conducted in C. neoformans. This project was initiated to study the molecular genetics of cell cycle associated genes in C. neoformans. In 1999, we reported a strain (B-4551)iaolated from chronic granulomatous lesion that exhibited aberrant cell morphology at 35 C and unable to multiply at 37 C. This strain fails to cause systemic infection in mice. Last year we identified the genetic defect in this strain and isolated the CCN1 gene which can complement the mutant phenotype (Ts)in vitro and allows the mutant to cause systemic fatal infection in mice. The CCN1 gene encodes a protein containing 16 tetratricopeptide repeats (TPR) of 34 amino acids each that show high homology with two essential genes, CRN of Drosophila and CLF1 of yeast. The CRN is involved in neurogenesis and the CLF1 gene encodes a spliceosome assembly protein. This year we attempted to identify the function of CCN1. The gene was introduced into a yeast CLF1 mutant. The strain B-4551 was also transformed with CLF1 gene to determine if they are orthologs. Although the S. cerevisiae gene complemented the B-4551 mutant phenotype, CCN1 failed to complement the clf1 mutant of yeast. The association of CCN1 and spliceosome assembly was investigated by using the GPD gene which contains several introns. The Northern analysis suggested that the gene is not directly associated with splicing of introns.
| Lee, Hyeseung; Chang, Yun C; Nardone, Glenn et al. (2007) TUP1 disruption in Cryptococcus neoformans uncovers a peptide-mediated density-dependent growth phenomenon that mimics quorum sensing. Mol Microbiol 64:591-601 |
| Lee, Hyeseung; Chang, Yun C; Kwon-Chung, K J (2005) TUP1 disruption reveals biological differences between MATa and MATalpha strains of Cryptococcus neoformans. Mol Microbiol 55:1222-32 |
| Chung, Seyung; Mondon, Philippe; Chang, Yun C et al. (2003) Cryptococcus neoformans with a mutation in the tetratricopeptide repeat-containing gene, CCN1, causes subcutaneous lesions but fails to cause systemic infection. Infect Immun 71:1988-94 |
| Bemis, D A; Krahwinkel, D J; Bowman, L A et al. (2000) Temperature-sensitive strain of Cryptococcus neoformans producing hyphal elements in a feline nasal granuloma. J Clin Microbiol 38:926-8 |
