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The biology of mating in Candida albicans

Nature Reviews Microbiology volume 1, pages 106–116 (2003)Cite this article

Key Points

  • In 2000, the view of Candida albicans as a purely asexual organism was overturned when C. albicans was shown to mate, both in a mouse host and on laboratory media. C. albicans has a highly efficient mating apparatus, which seems to have remained hidden from investigators.

  • In Saccharomyces cerevisiae, the mating locus called the MAT locus — encodes transcriptional regulatory proteins that are responsible for controlling the sexual cycle. The genes residing at the MAT locus can be either the a type or the α type. In C. albicans the mating locus — called the MTL (mating-type-like) locus — is much larger than the MAT locus of S. cerevisiae and contains more genes. However, the MTL locus does have orthologues of the S. cerevisiae MATa1, MATα2 and MATα1 genes, and these control mating in C. albicans. Similar to S. cerevisiae the C. albicans locus can be can be either the a type or the α type.

  • In C. albicans, a cells mate with α cells, but to do so, they must first undergo a switch from the white from to the opaque from. This transition involves changes in expression of several hundred genes. White-opaque awitching is controlled by the mating-type locus, and a and α, but not a/α cells, can undergo switching.White and opaque cells have different virulence profiles in an animal model, and this link between mating and virulence indicates that white-opaque switching (which is conspicuously absent in S. cerevisiae mating) might be a strategy to allow mating in the hostile environment of a mammalian host.

  • C. albicans is diploid, and a successful mating event produces an a/α (non-mating) tetraploid cell. These tetraploids can lose chromosomes in an apparently concerted manner, to become diploid (or at least near-diploid) a and α mating-competent cells. So, in C. albicans, chromosome loss might provide an alternative to meiosis thereby completing a parasexual cycle.

  • Important, but largely unanswered questions, are discussed, namely why is white-opaque switching a part of mating? What other aspects of C. albicans biology might the MTL locus control? What might be the purpose of mating in this human fungal pathogen?

Abstract

Candida albicans has maintained an elaborate — but largely hidden — mating apparatus, which shares some features with the closely related 'model' yeast Saccharomyces cerevisiae, but which also has some important differences. The differences are particularly noteworthy, as they could indicate the strategies that allow C. albicans to survive and mate in the hostile environment of a mammalian host. Indeed, some features of C. albicans mating seem to be intimately connected to its host.

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Figure 1: Cell-type determination in Saccharomyces cerevisiae.
Figure 2: Comparison of the S. cerevisiae and the C. albicans mating type loci.
Figure 3: Construction of the strains used to show mating in Candida albicans.
Figure 4: White and opaque cells of C. albicans.
Figure 5: The steps in C. albicans mating.
Figure 6: A diploid–tetraploid cycle for Candida albicans.
Figure 7: Generating diversity during infection.

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References

  1. Odds, F. C. in Candida and Candidosis. (Bailliere Tindall, London, UK, 1988). Beautifully written account of Candida research up to the late 1980s.

    Google Scholar 

  2. Calderone, R. A. in Candida and Candidiasis. (ed. Calderone, R. A.) 3–13 (ASM Press, Washington DC, 2002).

    Google Scholar 

  3. Tibayrenc, M. Are Candida albicans natural populations subdivided? Trends Microbiol. 5, 253–254 (1997).

    Article  CAS  Google Scholar 

  4. Vilgalys, R., Graser, Y., Schonian, G. & Presber, W. Is Candida albicans clonal or recombining? Trends Microbiol. 5, 254–257 (1997). References 3 and 4 summarize the conclusions regarding sexual recombination reached from population studies of C. albicans.

    Article  Google Scholar 

  5. Xu, J. & Mitchell, T. G. in Candida and Candidiasis. (ed. Calderone, R. A.) 55–64 (ASM Press, Washington DC, 2002).

    Google Scholar 

  6. Whelan, W. L. The genetics of medically important fungi. CRC Critical Reviews in Microbiology 14, 99–170 (1987).

    Article  CAS  Google Scholar 

  7. Ayala, F.J. Is sex better? Parasites say 'no'. Proc. Natl Acad. Sci USA 95, 3346–3348 (1998).

    Article  CAS  Google Scholar 

  8. Hull, C. M., Raisner, R. M. & Johnson, A. D. Evidence for mating of the 'asexual' yeast Candida albicans in a mammalian host. Science 289, 307–310 (2000).

    Article  CAS  Google Scholar 

  9. Magee, B. B. & Magee, P. T. Induction of mating in Candida albicans by construction of MTLa and MTLα strains. Science 289, 310–313 (2000). References 8 and 9 are the first reports of mating in C. albicans.

    Article  CAS  Google Scholar 

  10. Gargas, A., DePriest, P. T., Grube, M. & Tehler, A. Multiple origins of lichen symbioses in fungi suggested by SSU rDNA phylogeny. Science 268: 1492–1495 (1995).

    Article  CAS  Google Scholar 

  11. Hedges, S. B. The origin and evolution of model organisms. Nature Rev. Genet. 3, 838–849 (2002).

    Article  CAS  Google Scholar 

  12. Goffeau, A. et al. Life with 6000 genes. Science 274, 546–567 (1996).

    Article  CAS  Google Scholar 

  13. Kellis, M., Patterson, N., Endrizzi, M., Birren, B. & Lander, E. S. Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241–254 (2003).

    Article  CAS  Google Scholar 

  14. Magee, P. T. & Chibana, H. in Candida and Candidiasis. (ed. Calderone, R. A.) 293–304 (ASM Press, Washington DC, 2002).

    Google Scholar 

  15. Kadosh, D. and Johnson, A. D. Rfg1, a protein related to the Saccharomyces cerevisiae hypoxic regulator Rox1, controls filamentous growth and virulence in Candida albicans. Mol. Cell Biol. 21, 2496–2505 (2001).

    Article  CAS  Google Scholar 

  16. Khalaf, R. A. & Zitomer, R. S. The DNA-binding protein Rfg1 is a repressor of filamentation in Candida albicans. Genetics 157, 1503–1512 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Olaiya, A. F. & Sogin, S. J. Ploidy determination of Candida albicans. J. Bacteriol. 140, 1043–1049 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Whelen, W. L. & Magee, P. T. Natural heterozygosity in Candida albicans. Mol Gen Genet. 180, 107–113 (1981).

    Article  Google Scholar 

  19. Riggsby, W. S., Torres-Bauza, L. J., Wills, J. W. & Townes, T. M. DNA content, kinetic complexity, and the ploidy question in Candida albicans. Mol. Cell Biol. 2, 853–862 (1982).

    Article  CAS  Google Scholar 

  20. Berman, J. & Sudbery, P. E. Candida albicans: A molecular revolution built on lessons from budding yeast. Nature 3, 918–930 (2002). Excellent review of recent developments in C. albicans research.

    CAS  Google Scholar 

  21. Scherer, S. in Candida and Candidiasis. (ed. Calderone, R. A.) 259–265 (ASM Press, Washington DC, 2002).

    Google Scholar 

  22. Yesland, K. & Fonzi, W. A. Allele-specific gene targeting in Candida albicans results from heterology between alleles. Microbiology 146, 2097–2104 (2000).

    Article  CAS  Google Scholar 

  23. Herskowitz, I., Rine, J. & Strathern, J. in The Molecular Cellular Biology of the Yeast Saccharomyces. (eds Jones, E. W., Pringle, J. R. & Broach, J. R.) Vol. 2 (Cold Spring Harbor Laboratory Press, New York, 1992).

    Google Scholar 

  24. Johnson, A. D. Molecular mechanisms of cell-type determination in budding yeast. Curr. Opin. Genet. Dev. 5, 552–558 (1995).

    Article  CAS  Google Scholar 

  25. Sadhu, C., Hoekstra, D., McEachern, M. J., Reed, S. I. & Hicks, J. B. A G-protein α-subunit from asexual Candida albicans functions in the mating signal transduction pathway of Saccharomyces cerevisiae and is regulated by the a1-α2 repressor. Mol. Cell Biol. 12, 1977–1985 (1992).

    Article  CAS  Google Scholar 

  26. Liu, H., Kohler, J. & Fink, G. R. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266, 1723–1726 (1994).

    Article  CAS  Google Scholar 

  27. Clark, K. L. et al. Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans. Mol. Gen. Genet. 249, 609–621 (1995).

    Article  CAS  Google Scholar 

  28. Diener, A. C. & Fink, G. R. DLH1 is a functional Candida albicans homologue of the meiosis-specific gene DMC1. Genetics 143, 769–776 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Leberer, E. et al. Signal transduction through homologs of the Ste20p and Ste7p protein kinase hyphal formation in the pathogenic fungus Candida albicans. Proc. Natl Acad. Sci. USA 93, 13217–13222 (1996).

    Article  CAS  Google Scholar 

  30. Raymond, M. et al. A Ste6p/P-glycoprotein homologue from the asexual yeast Candida albicans transports the a-factor mating pheromone in Saccharomyces cerevisiae. Mol. Microbiol. 27, 587–598 (1998).

    Article  CAS  Google Scholar 

  31. Hull, C. M. & Johnson, A. D. Identification of a mating type-like locus in the asexual pathogenic yeast Candida albicans. Science 285, 1271–1275 (1999). Description of the C. albicans mating-type-like ( MTL ) locus.

    Article  CAS  Google Scholar 

  32. Odds, F. C., Brown, A. J. & Gow, N. A. Might Candida albicans be made to mate after all? Trends Microbiol. 8, 4–6 (2000).

    Article  CAS  Google Scholar 

  33. Fonzi, W. A. & Irwin, M. Y. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717–728 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Janbon, G., Sherman, F. & Rustchenko, E. Monosomy of a specific chromosome determines L-sorbose utilization: a novel regulatory mechanism in Candida albicans. Proc. Natl Acad. Sci. USA 95, 5150–5155 (1998).

    Article  CAS  Google Scholar 

  35. Janbon, G., Sherman, F. & Rustchenko, E. Appearance and properties of L-sorbose-utilizing mutants of Candida albicans obtained on a selective plate. Genetics 153, 653–664 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Gow, N. A., Brown, A. J. & Odds, F. C. Candida's arranged marriage. Science 289, 256–257 (2000).

    Article  CAS  Google Scholar 

  37. Soll, D. R. in Candida and Candidiasis. (ed. Calderone, R. A.) 123–142 (ASM Press, Washington DC, 2002).

    Google Scholar 

  38. Soll, D. R., Lockhart, S. & Zhao, R. The relationship between switching and mating in Candida albicans. Eukaryot. Cell 2, 390–397 (2003).

    Article  CAS  Google Scholar 

  39. Srikantha, T., Tsai, L., Daniels, K., Klar, A. J. & Soll, D. R. The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans. J. Bacteriol. 183, 4614–4625 (2001).

    Article  CAS  Google Scholar 

  40. Lan, C. Y. et al. Metabolic specialization associated with phenotypic switching in Candida albicans. Proc. Natl Acad. Sci. USA 99, 14907–14912 (2002). Description of several hundred genes differentially expressed in white versus opaque cells.

    Article  CAS  Google Scholar 

  41. Slutsky, B. et al. 'White-opaque transition': a second high-frequency switching system in Candida albicans. J. Bacteriol. 169, 189–197 (1987). Original description of white-opaque switching.

    Article  CAS  Google Scholar 

  42. Miller, M. G. & Johnson, A. D. White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110, 293–302 (2002). First description of the role of white-opaque switching in mating.

    Article  CAS  Google Scholar 

  43. Lockhart, S. R. et al. In Candida albicans, white-opaque switchers are homozygous for mating type. Genetics 162, 737–745 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Gow, N. A. Candida albicans switches mates. Mol. Cell 10, 217–218 (2002).

    Article  CAS  Google Scholar 

  45. Sprague, G. F. Jr. in Guide to Yeast Genetics and Molecular Biology. (eds Guthrie, C. & Fink, G. R.) 77–93 (Academic Press, New York, 1991).

    Book  Google Scholar 

  46. Anderson, J., Mihalik, R. & Soll, D. R. Ultrastructure and antigenicity of the unique cell wall pimple of the Candida opaque phenotype. J. Bacteriol. 172, 224–235 (1990).

    Article  CAS  Google Scholar 

  47. Lockhart, S. R., Daniels, K. J., Zhao, R., Wessels, D. & Soll, D. R. Cell biology of mating in Candida albicans. Eukaryot. Cell. 2, 49–61 (2003). First visualization and description of the mating process in C. albicans.

    Article  CAS  Google Scholar 

  48. Sprague, G. F. J. & Thorner, J. W. in The Molecular and Cellular Biology of the Yeast Saccharomyces (eds Jones, E. W., Pringle, J. R. & Broach, J. R) 657–744 (Cold Spring Harbor Laboratory Press, New York, 1992).

    Google Scholar 

  49. MacKay, V. L. in The Early Days of Yeast Genetics. (eds Hall, M. N. & Linder, P.) (Cold Spring Harbor Laboratory Press, New York, 1993).

    Google Scholar 

  50. Dutcher, S. K. Internuclear transfer of genetic information in kar1-1/KAR1 heterokaryons in Saccharomyces cerevisiae. Mol. Cell. Biol. 1, 245–253 (1981).

    Article  CAS  Google Scholar 

  51. Chen, J., Chen, J., Lane, S. & Liu, H. A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol. Microbiol. 46: 1335–1344 (2002).

    Article  CAS  Google Scholar 

  52. Magee, B. B., Legrand, M., Alarco, A. M., Raymond, M. & Magee, P. T. Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol. Microbiol. 46, 1345–1351 (2002).

    Article  CAS  Google Scholar 

  53. Bennett, R. J. & Johnson, A. D. Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. EMBO J. 22, 2505–2515 (2003).

    Article  CAS  Google Scholar 

  54. Tzung, K. W. et al. Genomic evidence for a complete sexual cycle in Candida albicans. Proc. Natl Acad. Sci. USA 98, 3249–3253 (2001).

    Article  CAS  Google Scholar 

  55. Bennett, R. J., Uhl, M. A., Miller, M. G. & Johnson, A. D. Identification and characterization of a Candida albicans mating pheromone. Mol. Cell. Biol. (in the press).

  56. Madhani, H. D. & G. R., Fink. The control of filamentous differentiation and virulence in fungi. Trends Cell Biol. 8, 348–353 (1998). Excellent general review on the relationship of filamentous growth to virulence in fungi.

    Article  CAS  Google Scholar 

  57. Mitchell, A. P. Dimorphism and virulence in Candida albicans. Curr. Opin. Microbiol. 1, 687–692 (1998).

    Article  CAS  Google Scholar 

  58. Whiteway, M. Transcriptional control of cell type and morphogenesis in Candida albicans. Curr. Opin. Microbiol. 3, 582–588 (2000).

    Article  CAS  Google Scholar 

  59. Calderone, R. A. & Fonzi, W. A. Virulence factors of Candida albicans. Trends Microbiol. 9, 327–335 (2001).

    Article  CAS  Google Scholar 

  60. Navarro-Garcia, F., M. Sanchez, Nombela, C. & Pla, J. Virulence genes in the pathogenic yeast Candida albicans. FEMS Microbiol. Rev. 25, 245–268 (2001).

    Article  CAS  Google Scholar 

  61. Liu, H. Co-regulation of pathogenesis with dimorphism and phenotypic switching in Candida albicans, a commensal and a pathogen. Int. J. Med. Microbiol. 292, 299–311 (2002).

    Article  CAS  Google Scholar 

  62. Brown, A. J. P. in Candida and Candidiasis. (ed. Calderone, R. A.) 87–93 (ASM Press, Washington, DC, 2002).

    Google Scholar 

  63. Brown, A. J. P. in Candida and Candidiasis. (ed. Calderone, R. A.) 95–106 (ASM Press, Washington, DC, 2002).

    Google Scholar 

  64. Roberts, C. J. et al. Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. Science 287, 873–880 (2000).

    Article  CAS  Google Scholar 

  65. Rustchenko, E. & Sherman, F. in Pathogenic Fungi in Humans and Animals. (ed. Howard, D.) (Marcel Dekker, New York, 2003).

    Google Scholar 

  66. Hilton, C., Markie, D., Corner, B., Rikkerink, E. & Poulter, R. Heat shock induces chromosome loss in the yeast Candida albicans. Mol. Gen. Genet. 200, 162–168 (1985).

    Article  CAS  Google Scholar 

  67. Kolotila, M. P. & Diamond, R. D. Effects of neutrophils and in vitro oxidants on survival and phenotypic switching of Candida albicans WO-1. Infect. Immun. 58, 1174–1179 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Kvaal, C. et al. Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection. Infect. Immun. 67, 6652–6662 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lachke, S. A., Lockhart, S. R., Daniels, K. J. & Soll, D. R. Skin facilitates Candida albicans mating. Infect. Immun. 71, 4970–4976 (2003).

    Article  CAS  Google Scholar 

  70. Hoyer, L. L. The ALS gene family of Candida albicans. Trends Microbiol. 9, 176–180 (2001).

    Article  CAS  Google Scholar 

  71. Lehto, M. & Olkkonen, V. M. The OSBP-related proteins: a novel protein family involved in vesicle transport, cellular lipid metabolism, and cell signalling. Biochim. Biophys. Acta 1631, 1–11 (2003).

    Article  CAS  Google Scholar 

  72. Hama, H., Scheiders, E. A., Thorner, J., Takemoto, J. Y. & DeWald, D. B. Direct involvement of phosphatidylinositol 4-phosphate in secretion in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 274, 34294–34300 (1999).

    Article  CAS  Google Scholar 

  73. Audhya, A., Foti, M. & Emr, S. D. Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Mol. Biol. Cell 11, 2673–2689 (2000).

    Article  CAS  Google Scholar 

  74. Lengeler, K. B. et al. Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes. Eukaryot. Cell 1, 704–718 (2002).

    Article  CAS  Google Scholar 

  75. Peck, J. R. & Waxman, D. Mutation and sex in a competitive world. Nature 406, 399–404 (2000).

    Article  CAS  Google Scholar 

  76. Graser, Y. et al. Molecular markers reveal that population structure of the human pathogen Candida albicans exhibits both clonality and recombination. Proc. Natl Acad. Sci. USA 93, 12473–12477 (1996).

    Article  CAS  Google Scholar 

  77. Anderson, J. B. et al. Infrequent genetic exchange and recombination in the mitochondrial genome of Candida albicans. J. Bacteriol. 183, 865–872 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

The author thanks M. Chiu, M. Miller, A. Tsong and R. Zordan for critical comments and for help in preparing the manuscript and figures. Sequence data for Candida albicans was obtained from the Stanford Genome Technology Center (see Online links). Sequencing of Candida albicans was accomplished with the support of the NIDR and the Burroughs Wellcome fund. The author gratefully acknowledges the valuable comments made by the anonymous reviewers.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of California, San Francisco, Mission Bay Genentech Hall, 600 16th Street, San Francisco, 94143-2200, California, USA

    Alexander Johnson

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DATABASES

Entrez

CPH1

CST20

genome of S. cerevisiae

HST7

Mata1

Matα1

Matα2

MFa1

OBPα

PAPα

PIKα

STE2

STE6

Infectious Disease Information

candidiasis

entry 2

FURTHER INFORMATION

Stanford Genome Technology Center

Glossary

HOMEODOMAIN

A 60 amino acid protein domain that folds into a compact three-helix structure and binds to specific sequences of DNA. Homeodomain proteins are found in virtually all eukaryotes, where they specify cell identity.

HETEROKARYON

A cell that has two or more genetically distinct nuclei.

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Johnson, A. The biology of mating in Candida albicans. Nat Rev Microbiol 1, 106–116 (2003). https://doi.org/10.1038/nrmicro752

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