User:Ilya/Yeast/Phylogeny/Cryptococcus neoformans

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  • a fungal pathogen that causes meningitis in immunocompromised patients

pathogenic basidiomycete Cryptococcus neoformans has two mating type specific STE12 genes STE12a and STE12α which play different roles in haploid fruiting mating and the regulation of genes [1]

C. neoformans causes meningoencephalitis in humans and animals Strains of the fungus exist in five serotypes (A, B, C, D and AD) and the WM276 strain represents the serotype B group. In general, cryptococcal infections occur at high frequency (10 - 25%) in immunocompromised people such as those individuals infected with the human immunodeficiency virus (HIV). However, serotype B strains also infect immunocompetent (otherwise healthy) people. GSC - C. neoformans summary

It is a heterothallic yeast-like basidiomycete with two mating types, MATalpha and MAT a The S. cerevisiae pheromone response pathway appears to be conserved in C. neoformans. Preliminary molecular studies of mating in C. neoformans have identified a number of genes bearing substantial sequence similarity to S. cerevisiae mating-associated genes. These genes include homologues of GPA1 [2, 3], GPB1 [4], STE12 [5], STE4 (Wang et al., 2000) and a pheromone (Moore and Edman, 1993). [6]

Additionally, a phenotype that parallels the S. cerevisiae pseudohyphal response has been identified in C. neoformans. [6]

In spite of the fact that the C. neoformans mating pathway appears to be conserved, which is noteworthy because of the phylogenetic distance from S. cerevisiae, the importance of mating and mating type in this organism lies in virulence. Regardless of serotype or geographical location, the overwhelming majority of C. neoformans infections are caused by the MATalpha mating type [6]. This may be due to the overwhelming prevalence of MATalpha in the evironment [7]. In C. neoformans var. grubii it appears that the mating type is not linked to virulence [8] in contrast to results in C. neoformans var. neoformans [9]. The prevalence of MATalpha individuals in nature may be due to the haploid fruiting which can occur in haploid MATalpha cells [10].


  1. Calcagno AM, Bignell E, Warn P, Jones MD, Denning DW, Mühlschlegel FA, Rogers TR, and Haynes K. Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation. Mol Microbiol. 2003 Nov;50(4):1309-18. DOI:10.1046/j.1365-2958.2003.03755.x | PubMed ID:14622417 | HubMed [1]
  2. Tolkacheva T, McNamara P, Piekarz E, and Courchesne W. Cloning of a Cryptococcus neoformans gene, GPA1, encoding a G-protein alpha-subunit homolog. Infect Immun. 1994 Jul;62(7):2849-56. DOI:10.1128/iai.62.7.2849-2856.1994 | PubMed ID:8005675 | HubMed [Tolkacheva1994]
  3. Alspaugh JA, Perfect JR, and Heitman J. Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP. Genes Dev. 1997 Dec 1;11(23):3206-17. DOI:10.1101/gad.11.23.3206 | PubMed ID:9389652 | HubMed [Alspaugh1997]
  4. Wang P, Perfect JR, and Heitman J. The G-protein beta subunit GPB1 is required for mating and haploid fruiting in Cryptococcus neoformans. Mol Cell Biol. 2000 Jan;20(1):352-62. DOI:10.1128/MCB.20.1.352-362.2000 | PubMed ID:10594037 | HubMed [Wang2000]
  5. Wickes BL, Edman U, and Edman JC. The Cryptococcus neoformans STE12alpha gene: a putative Saccharomyces cerevisiae STE12 homologue that is mating type specific. Mol Microbiol. 1997 Dec;26(5):951-60. DOI:10.1046/j.1365-2958.1997.6322001.x | PubMed ID:9426132 | HubMed [Wickes1997]
  6. Clarke DL, Woodlee GL, McClelland CM, Seymour TS, and Wickes BL. The Cryptococcus neoformans STE11alpha gene is similar to other fungal mitogen-activated protein kinase kinase kinase (MAPKKK) genes but is mating type specific. Mol Microbiol. 2001 Apr;40(1):200-13. DOI:10.1046/j.1365-2958.2001.02375.x | PubMed ID:11298287 | HubMed [2]
  7. Litvintseva AP, Marra RE, Nielsen K, Heitman J, Vilgalys R, and Mitchell TG. Evidence of sexual recombination among Cryptococcus neoformans serotype A isolates in sub-Saharan Africa. Eukaryot Cell. 2003 Dec;2(6):1162-8. DOI:10.1128/EC.2.6.1162-1168.2003 | PubMed ID:14665451 | HubMed [Litvintseva2003]
  8. Nielsen K, Marra RE, Hagen F, Boekhout T, Mitchell TG, Cox GM, and Heitman J. Interaction between genetic background and the mating-type locus in Cryptococcus neoformans virulence potential. Genetics. 2005 Nov;171(3):975-83. DOI:10.1534/genetics.105.045039 | PubMed ID:15965241 | HubMed [Nielsen2005]
  9. Kwon-Chung KJ, Edman JC, and Wickes BL. Genetic association of mating types and virulence in Cryptococcus neoformans. Infect Immun. 1992 Feb;60(2):602-5. DOI:10.1128/iai.60.2.602-605.1992 | PubMed ID:1730495 | HubMed [Kwon-Chung1992]
  10. Hull CM and Heitman J. Genetics of Cryptococcus neoformans. Annu Rev Genet. 2002;36:557-615. DOI:10.1146/annurev.genet.36.052402.152652 | PubMed ID:12429703 | HubMed [Hull2002]
  11. Lin X, Huang JC, Mitchell TG, and Heitman J. Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATalpha allele enhances filamentation. PLoS Genet. 2006 Nov 17;2(11):e187. DOI:10.1371/journal.pgen.0020187 | PubMed ID:17112316 | HubMed [Lin2006]

All Medline abstracts: PubMed | HubMed