The Cryptococcus neoformans genome sequencing project

Cryptococcus neoformans is a basidiomycete that can cause life-threatening meningoencephalitis in patients with and without impaired immune function. Cryptococcosis is usually an opportunistic infection in patients with compromised immunity as a consequence of HIV-1 infection, steroid administration, cancer chemotherapy, sarcoidosis, diabetes, or inherited immune system defects. This pathogenic yeast has a defined sexual cycle, which allows classical genetic analysis. Molecular biology approaches, including transformation and gene disruption by homologous recombination, and animal models for studies of virulence are both well developed. Recently an international consortium convened to begin the C. neoformans genome sequencing project, and we review here background and arguments for this project. We also discuss the importance of this project to the biology and virulence of this organism in particular, and to virulence in general.

[1]  K. Kwon-Chung,et al.  Isolation of the URA5 gene from Cryptococcus neoformans var. neoformans and its use as a selective marker for transformation , 1990, Molecular and cellular biology.

[2]  J. Perfect,et al.  Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. , 1985, The Journal of clinical investigation.

[3]  H. Mewes,et al.  Overview of the yeast genome. , 1997, Nature.

[4]  J. Heitman,et al.  On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans. , 1999, Fungal genetics and biology : FG & B.

[5]  B. Wickes,et al.  The Cryptococcus neoformans STE12α gene: a putative Saccharomyces cerevisiae STE12 homologue that is mating type specific , 1997, Molecular microbiology.

[6]  A. Casadevall,et al.  Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants , 1994, Infection and immunity.

[7]  J. Edman,et al.  The alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene , 1993, Molecular and cellular biology.

[8]  A. Casadevall,et al.  Expression of inducible nitric oxide synthase in rat pulmonary Cryptococcus neoformans granulomas. , 1996, The American journal of pathology.

[9]  S Falkow,et al.  Molecular Koch's postulates applied to microbial pathogenicity. , 1988, Reviews of infectious diseases.

[10]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[11]  E. Anaissie,et al.  Regulation of cryptococcal capsular polysaccharide by iron. , 1993, The Journal of infectious diseases.

[12]  J. Heitman,et al.  Comparison of the Roles of Calcineurin in Physiology and Virulence in Serotype D and Serotype A Strains ofCryptococcus neoformans , 2000, Infection and Immunity.

[13]  J. Heitman,et al.  Morphogenesis of Cryptococcus neoformans. , 2000, Contributions to microbiology.

[14]  S. Oliver,et al.  Erratum: Overview of the yeast genome , 1997, Nature.

[15]  A. Casadevall,et al.  Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with changes in virulence and pulmonary inflammatory response in rodents. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Perfect,et al.  Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA , 1993, Journal of bacteriology.

[17]  J. Heitman,et al.  The STE12alpha homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans. , 1999, Genetics.

[18]  M. Krockenberger,et al.  Presence of α and a Mating Types in Environmental and Clinical Collections of Cryptococcus neoformans var. gattii Strains from Australia , 1999, Journal of Clinical Microbiology.

[19]  A. Casadevall,et al.  Persistent Cryptococcus neoformansPulmonary Infection in the Rat Is Associated with Intracellular Parasitism, Decreased Inducible Nitric Oxide Synthase Expression, and Altered Antibody Responsiveness to Cryptococcal Polysaccharide , 2000, Infection and Immunity.

[20]  Andrew Smith.  Genome sequence of the nematode C-elegans: A platform for investigating biology , 1998 .

[21]  J. Perfect,et al.  A Glucan Synthase FKS1 Homolog inCryptococcus neoformans Is Single Copy and Encodes an Essential Function , 1999, Journal of bacteriology.

[22]  J. Heitman,et al.  The G-Protein β Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans , 2000, Molecular and Cellular Biology.

[23]  N. Vietri,et al.  Identification and characterization of a trans-activator involved in the regulation of encapsulation by Bacillus anthracis. , 1995, Gene.

[24]  J. Heitman,et al.  Signal transduction pathways regulating differentiation and pathogenicity of Cryptococcus neoformans. , 1998, Fungal genetics and biology : FG & B.

[25]  B. Wickes,et al.  Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Perfect,et al.  The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid , 1993, Infection and immunity.

[27]  J. Lodge,et al.  Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. Casadevall,et al.  Molecular epidemiology of Cryptococcus neoformans in Brazil and the United States: evidence for both local genetic differences and a global clonal population structure , 1997, Journal of clinical microbiology.

[29]  K. Buchanan,et al.  What makes Cryptococcus neoformans a pathogen? , 1998, Emerging infectious diseases.

[30]  J. Heitman,et al.  Topoisomerase I is essential in Cryptococcus neoformans: role In pathobiology and as an antifungal target. , 1999, Genetics.

[31]  A. Casadevall,et al.  The antibody response to fungal melanin in mice. , 1998, Journal of immunology.

[32]  J. Edman.  Isolation of telomerelike sequences from Cryptococcus neoformans and their use in high-efficiency transformation , 1992, Molecular and cellular biology.

[33]  T. Sorrell,et al.  Molecular typing of global isolates of Cryptococcus neoformans var. neoformans by polymerase chain reaction fingerprinting and randomly amplified polymorphic DNA — a pilot study to standardize techniques on which to base a detailed epidemiological survey , 1999, Electrophoresis.

[34]  B. Wickes,et al.  Cryptococcus neoformans STE12α Regulates Virulence but Is Not Essential for Mating , 2000, The Journal of experimental medicine.

[35]  J. Heitman,et al.  Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans. , 2000, Fungal genetics and biology : FG & B.

[36]  B. Wickes,et al.  Genetic association of mating types and virulence in Cryptococcus neoformans , 1992, Infection and immunity.

[37]  A. Casadevall,et al.  Melanization of Cryptococcus neoformansin Murine Infection , 1999, Molecular and Cellular Biology.

[38]  K. Kwon-Chung,et al.  DISTRIBUTION OF α AND α MATING TYPES OF CRYPTOCOCCUS NEOFORMANS AMONG NATURAL AND CLINICAL ISOLATES , 1978 .

[39]  A. Casadevall,et al.  Microevolution of a Standard Strain ofCryptococcus neoformans Resulting in Differences in Virulence and Other Phenotypes , 1998, Infection and Immunity.

[40]  J. Heitman,et al.  Signal transduction cascades regulating mating, filamentation, and virulence in Cryptococcus neoformans. , 1999, Current opinion in microbiology.

[41]  A. Hamilton,et al.  Virulence factors of Cryptococcus neoformans. , 1996, Current topics in medical mycology.

[42]  K. Kwon-Chung,et al.  Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans , 1986, Infection and immunity.

[43]  K. Kwon-Chung,et al.  A new species of Filobasidiella, the sexual state of Cryptococcus neoformans B and C serotypes. , 1976, Mycologia.

[44]  A. Casadevall,et al.  Cryptococcus neoformans var.grubii: Separate Varietal Status for Cryptococcus neoformans Serotype A Isolates , 1999, Journal of Clinical Microbiology.

[45]  J. Heitman,et al.  Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP. , 1997, Genes & development.

[46]  K. Kwon-Chung.  Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. , 1976, Mycologia.

[47]  K. Kwon-Chung,et al.  Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence , 1994, Molecular and cellular biology.

[48]  K. Kwon-Chung.  A new genus, filobasidiella, the perfect state of Cryptococcus neoformans. , 1975, Mycologia.

[49]  J. Perfect,et al.  Chronic cryptococcal meningitis: a new experimental model in rabbits. , 1980, The American journal of pathology.

[50]  J. Perfect,et al.  Effect of the laccase gene CNLAC1, on virulence of Cryptococcus neoformans , 1996, The Journal of experimental medicine.

[51]  J. Heitman,et al.  Calcineurin is required for virulence of Cryptococcus neoformans , 1997, The EMBO journal.

[52]  N. W. Davis,et al.  The complete genome sequence of Escherichia coli K-12. , 1997, Science.

[53]  J. Heitman,et al.  Rapamycin Antifungal Action Is Mediated via Conserved Complexes with FKBP12 and TOR Kinase Homologs inCryptococcus neoformans , 1999, Molecular and Cellular Biology.