This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nielsen, K.
Right arrow Articles by Heitman, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nielsen, K.
Right arrow Articles by Heitman, J.

 Previous Article  |  Next Article 

Infection and Immunity, September 2003, p. 4831-4841, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.4831-4841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sexual Cycle of Cryptococcus neoformans var. grubii and Virulence of Congenic a and {alpha} Isolates

Kirsten Nielsen,1,2 Gary M. Cox,1,3 Ping Wang,1,{dagger} Dena L. Toffaletti,3 John R. Perfect,1,3 and Joseph Heitman1,2,3,4*

Departments of Molecular Genetics and Microbiology,1 Medicine,3 Pharmacology and Cancer Biology,4 Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 277102

Received 21 March 2003/ Returned for modification 12 April 2003/ Accepted 28 April 2003

Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and {alpha} mating types has been reported for two varieties (C. neoformans var. neoformans, serotype D, and C. neoformans var. gattii, serotypes B and C), yet the vast majority of infections involve a distinct variety (C. neoformans var. grubii, serotype A) that has been thought to be clonal and restricted to the {alpha} mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a crg1 mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and {alpha} mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and {alpha} mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the {alpha} mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, 322 CARL Building, Research Dr., Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu.

Editor: T. R. Kozel

{dagger} Present address: Department of Pediatrics and Microbiology, Children's Hospital, New Orleans, LA 70118.

Infection and Immunity, September 2003, p. 4831-4841, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.4831-4841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Baker, L. G., Specht, C. A., Lodge, J. K. (2009). Chitinases Are Essential for Sexual Development but Not Vegetative Growth in Cryptococcus neoformans. Eukaryot Cell 8: 1692-1705 [Abstract] [Full Text]  
  • Velagapudi, R., Hsueh, Y.-P., Geunes-Boyer, S., Wright, J. R., Heitman, J. (2009). Spores as Infectious Propagules of Cryptococcus neoformans. Infect. Immun. 77: 4345-4355 [Abstract] [Full Text]  
  • Idnurm, A., Walton, F. J., Floyd, A., Reedy, J. L., Heitman, J. (2009). Identification of ENA1 as a Virulence Gene of the Human Pathogenic Fungus Cryptococcus neoformans through Signature-Tagged Insertional Mutagenesis. Eukaryot Cell 8: 315-326 [Abstract] [Full Text]  
  • Nichols, C. B., Ferreyra, J., Ballou, E. R., Alspaugh, J. A. (2009). Subcellular Localization Directs Signaling Specificity of the Cryptococcus neoformans Ras1 Protein. Eukaryot Cell 8: 181-189 [Abstract] [Full Text]  
  • Charlier, C., Nielsen, K., Daou, S., Brigitte, M., Chretien, F., Dromer, F. (2009). Evidence of a Role for Monocytes in Dissemination and Brain Invasion by Cryptococcus neoformans. Infect. Immun. 77: 120-127 [Abstract] [Full Text]  
  • Price, M. S., Nichols, C. B., Alspaugh, J. A. (2008). The Cryptococcus neoformans Rho-GDP Dissociation Inhibitor Mediates Intracellular Survival and Virulence. Infect. Immun. 76: 5729-5737 [Abstract] [Full Text]  
  • Moyrand, F., Lafontaine, I., Fontaine, T., Janbon, G. (2008). UGE1 and UGE2 Regulate the UDP-Glucose/UDP-Galactose Equilibrium in Cryptococcus neoformans. Eukaryot Cell 7: 2069-2077 [Abstract] [Full Text]  
  • Gerik, K. J., Bhimireddy, S. R., Ryerse, J. S., Specht, C. A., Lodge, J. K. (2008). PKC1 Is Essential for Protection against both Oxidative and Nitrosative Stresses, Cell Integrity, and Normal Manifestation of Virulence Factors in the Pathogenic Fungus Cryptococcus neoformans. Eukaryot Cell 7: 1685-1698 [Abstract] [Full Text]  
  • Hsueh, Y.-P., Fraser, J. A., Heitman, J. (2008). Transitions in Sexuality: Recapitulation of an Ancestral Tri- and Tetrapolar Mating System in Cryptococcus neoformans. Eukaryot Cell 7: 1847-1855 [Abstract] [Full Text]  
  • Lin, X., Nielsen, K., Patel, S., Heitman, J. (2008). Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans. Infect. Immun. 76: 2923-2938 [Abstract] [Full Text]  
  • Hiremath, S. S., Chowdhary, A., Kowshik, T., Randhawa, H. S., Sun, S., Xu, J. (2008). Long-distance dispersal and recombination in environmental populations of Cryptococcus neoformans var. grubii from India. Microbiology 154: 1513-1524 [Abstract] [Full Text]  
  • Rutherford, J. C., Lin, X., Nielsen, K., Heitman, J. (2008). Amt2 Permease Is Required To Induce Ammonium-Responsive Invasive Growth and Mating in Cryptococcus neoformans. Eukaryot Cell 7: 237-246 [Abstract] [Full Text]  
  • Bahn, Y.-S., Geunes-Boyer, S., Heitman, J. (2007). Ssk2 Mitogen-Activated Protein Kinase Kinase Kinase Governs Divergent Patterns of the Stress-Activated Hog1 Signaling Pathway in Cryptococcus neoformans. Eukaryot Cell 6: 2278-2289 [Abstract] [Full Text]  
  • Li, L., Shen, G., Zhang, Z.-G., Wang, Y.-L., Thompson, J. K., Wang, P. (2007). Canonical Heterotrimeric G Proteins Regulating Mating and Virulence of Cryptococcus neoformans. Mol. Biol. Cell 18: 4201-4209 [Abstract] [Full Text]  
  • Fan, W., Idnurm, A., Breger, J., Mylonakis, E., Heitman, J. (2007). Eca1, a Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans. Infect. Immun. 75: 3394-3405 [Abstract] [Full Text]  
  • Gutierrez, A. L., Farage, L., Melo, M. N, Mohana-Borges, R. S, Guerardel, Y., Coddeville, B., Wieruszeski, J.-M., Mendonca-Previato, L., Previato, J. O (2007). Characterization of glycoinositolphosphoryl ceramide structure mutant strains of Cryptococcus neoformans. Glycobiology 17: 1C-1C [Abstract] [Full Text]  
  • Nielsen, K., De Obaldia, A. L., Heitman, J. (2007). Cryptococcus neoformans Mates on Pigeon Guano: Implications for the Realized Ecological Niche and Globalization. Eukaryot Cell 6: 949-959 [Abstract] [Full Text]  
  • Baker, L. G., Specht, C. A., Donlin, M. J., Lodge, J. K. (2007). Chitosan, the Deacetylated Form of Chitin, Is Necessary for Cell Wall Integrity in Cryptococcus neoformans. Eukaryot Cell 6: 855-867 [Abstract] [Full Text]  
  • Hicks, J. K., Heitman, J. (2007). Divergence of Protein Kinase A Catalytic Subunits in Cryptococcus neoformans and Cryptococcus gattii Illustrates Evolutionary Reconfiguration of a Signaling Cascade. Eukaryot Cell 6: 413-420 [Abstract] [Full Text]  
  • Idnurm, A., Giles, S. S., Perfect, J. R., Heitman, J. (2007). Peroxisome Function Regulates Growth on Glucose in the Basidiomycete Fungus Cryptococcus neoformans. Eukaryot Cell 6: 60-72 [Abstract] [Full Text]  
  • Palmer, D. A., Thompson, J. K., Li, L., Prat, A., Wang, P. (2006). Gib2, A Novel Gbeta-like/RACK1 Homolog, Functions as a Gbeta Subunit in cAMP Signaling and Is Essential in Cryptococcus neoformans. J. Biol. Chem. 281: 32596-32605 [Abstract] [Full Text]  
  • Kavanaugh, L. A., Fraser, J. A., Dietrich, F. S. (2006). Recent Evolution of the Human Pathogen Cryptococcus neoformans by Intervarietal Transfer of a 14-Gene Fragment. Mol Biol Evol 23: 1879-1890 [Abstract] [Full Text]  
  • Giles, S. S., Stajich, J. E., Nichols, C., Gerrald, Q. D., Alspaugh, J. A., Dietrich, F., Perfect, J. R. (2006). The Cryptococcus neoformans Catalase Gene Family and Its Role in Antioxidant Defense.. Eukaryot Cell 5: 1447-1459 [Abstract] [Full Text]  
  • Walton, F. J., Heitman, J., Idnurm, A. (2006). Conserved Elements of the RAM Signaling Pathway Establish Cell Polarity in the Basidiomycete Cryptococcus neoformans in a Divergent Fashion from Other Fungi. Mol. Biol. Cell 17: 3768-3780 [Abstract] [Full Text]  
  • Clancy, C. J., Nguyen, M. H., Alandoerffer, R., Cheng, S., Iczkowski, K., Richardson, M., Graybill, J. R. (2006). Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors.. Microbiology 152: 2247-2255 [Abstract] [Full Text]  
  • Cramer, K. L., Gerrald, Q. D., Nichols, C. B., Price, M. S., Alspaugh, J. A. (2006). Transcription Factor Nrg1 Mediates Capsule Formation, Stress Response, and Pathogenesis in Cryptococcus neoformans.. Eukaryot Cell 5: 1147-1156 [Abstract] [Full Text]  
  • Rydholm, C., Szakacs, G., Lutzoni, F. (2006). Low Genetic Variation and No Detectable Population Structure in Aspergillus fumigatus Compared to Closely Related Neosartorya Species.. Eukaryot Cell 5: 650-657 [Abstract] [Full Text]  
  • Litvintseva, A. P., Thakur, R., Vilgalys, R., Mitchell, T. G. (2006). Multilocus Sequence Typing Reveals Three Genetic Subpopulations of Cryptococcus neoformans var. grubii (Serotype A), Including a Unique Population in Botswana. Genetics 172: 2223-2238 [Abstract] [Full Text]  
  • Mogensen, E. G., Janbon, G., Chaloupka, J., Steegborn, C., Fu, M. S., Moyrand, F., Klengel, T., Pearson, D. S., Geeves, M. A., Buck, J., Levin, L. R., Muhlschlegel, F. A. (2006). Cryptococcus neoformans Senses CO2 through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1. Eukaryot Cell 5: 103-111 [Abstract] [Full Text]  
  • Tang, R. J., Breger, J., Idnurm, A., Gerik, K. J., Lodge, J. K., Heitman, J., Calderwood, S. B., Mylonakis, E. (2005). Cryptococcus neoformans Gene Involved in Mammalian Pathogenesis Identified by a Caenorhabditis elegans Progeny-Based Approach. Infect. Immun. 73: 8219-8225 [Abstract] [Full Text]  
  • Ibrahim, A. S., Magee, B. B., Sheppard, D. C., Yang, M., Kauffman, S., Becker, J., Edwards, J. E. Jr., Magee, P. T. (2005). Effects of Ploidy and Mating Type on Virulence of Candida albicans. Infect. Immun. 73: 7366-7374 [Abstract] [Full Text]  
  • Nielsen, K., Marra, R. E., Hagen, F., Boekhout, T., Mitchell, T. G., Cox, G. M., Heitman, J. (2005). Interaction Between Genetic Background and the Mating-Type Locus in Cryptococcus neoformans Virulence Potential. Genetics 171: 975-983 [Abstract] [Full Text]  
  • Nielsen, K., Cox, G. M., Litvintseva, A. P., Mylonakis, E., Malliaris, S. D., Benjamin, D. K. Jr., Giles, S. S., Mitchell, T. G., Casadevall, A., Perfect, J. R., Heitman, J. (2005). Cryptococcus neoformans {alpha} Strains Preferentially Disseminate to the Central Nervous System during Coinfection. Infect. Immun. 73: 4922-4933 [Abstract] [Full Text]  
  • Campbell, L. T., Fraser, J. A., Nichols, C. B., Dietrich, F. S., Carter, D., Heitman, J. (2005). Clinical and Environmental Isolates of Cryptococcus gattii from Australia That Retain Sexual Fecundity. Eukaryot Cell 4: 1410-1419 [Abstract] [Full Text]  
  • Mylonakis, E., Moreno, R., El Khoury, J. B., Idnurm, A., Heitman, J., Calderwood, S. B., Ausubel, F. M., Diener, A. (2005). Galleria mellonella as a Model System To Study Cryptococcus neoformans Pathogenesis. Infect. Immun. 73: 3842-3850 [Abstract] [Full Text]  
  • Bahn, Y.-S., Kojima, K., Cox, G. M., Heitman, J. (2005). Specialization of the HOG Pathway and Its Impact on Differentiation and Virulence of Cryptococcus neoformans. Mol. Biol. Cell 16: 2285-2300 [Abstract] [Full Text]  
  • Litvintseva, A. P., Kestenbaum, L., Vilgalys, R., Mitchell, T. G. (2005). Comparative Analysis of Environmental and Clinical Populations of Cryptococcus neoformans. J. Clin. Microbiol. 43: 556-564 [Abstract] [Full Text]  
  • Bahn, Y.-S., Hicks, J. K., Giles, S. S., Cox, G. M., Heitman, J. (2004). Adenylyl Cyclase-Associated Protein Aca1 Regulates Virulence and Differentiation of Cryptococcus neoformans via the Cyclic AMP-Protein Kinase A Cascade. Eukaryot Cell 3: 1476-1491 [Abstract] [Full Text]  
  • Moyrand, F., Janbon, G. (2004). UGD1, Encoding the Cryptococcus neoformans UDP-Glucose Dehydrogenase, Is Essential for Growth at 37{degrees}C and for Capsule Biosynthesis. Eukaryot Cell 3: 1601-1608 [Abstract] [Full Text]  
  • Nichols, C. B., Fraser, J. A., Heitman, J. (2004). PAK Kinases Ste20 and Pak1 Govern Cell Polarity at Different Stages of Mating in Cryptococcus neoformans. Mol. Biol. Cell 15: 4476-4489 [Abstract] [Full Text]  
  • Wang, P., Cutler, J., King, J., Palmer, D. (2004). Mutation of the Regulator of G Protein Signaling Crg1 Increases Virulence in Cryptococcus neoformans. Eukaryot Cell 3: 1028-1035 [Abstract] [Full Text]  
  • Hull, C. M., Cox, G. M., Heitman, J. (2004). The {alpha}-Specific Cell Identity Factor Sxi1{alpha} Is Not Required for Virulence of Cryptococcus neoformans. Infect. Immun. 72: 3643-3645 [Abstract] [Full Text]  
  • Marra, R. E., Huang, J. C., Fung, E., Nielsen, K., Heitman, J., Vilgalys, R., Mitchell, T. G. (2004). A Genetic Linkage Map of Cryptococcus neoformans variety neoformans Serotype D (Filobasidiella neoformans). Genetics 167: 619-631 [Abstract] [Full Text]  
  • Idnurm, A., Reedy, J. L., Nussbaum, J. C., Heitman, J. (2004). Cryptococcus neoformans Virulence Gene Discovery through Insertional Mutagenesis. Eukaryot Cell 3: 420-429 [Abstract] [Full Text]  
  • Litvintseva, A. P., Marra, R. E., Nielsen, K., Heitman, J., Vilgalys, R., Mitchell, T. G. (2003). Evidence of Sexual Recombination among Cryptococcus neoformans Serotype A Isolates in Sub-Saharan Africa. Eukaryot Cell 2: 1162-1168 [Abstract] [Full Text]  
  • Fraser, J. A., Subaran, R. L., Nichols, C. B., Heitman, J. (2003). Recapitulation of the Sexual Cycle of the Primary Fungal Pathogen Cryptococcus neoformans var. gattii: Implications for an Outbreak on Vancouver Island, Canada. Eukaryot Cell 2: 1036-1045 [Abstract] [Full Text]  
  • Mitchell, A. P. (2003). Updated View of Cryptococcus neoformans Mating Type and Virulence. Infect. Immun. 71: 4829-4830 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»