Article | Published:

The ‘obligate diploid’ Candida albicans forms mating-competent haploids

Nature volume 494, pages 5559 (07 February 2013) | Download Citation

  • A Corrigendum to this article was published on 18 November 2015

Abstract

Candida albicans, the most prevalent human fungal pathogen, is considered to be an obligate diploid that carries recessive lethal mutations throughout the genome. Here we demonstrate that C. albicans has a viable haploid state that can be derived from diploid cells under in vitro and in vivo conditions, and that seems to arise through a concerted chromosome loss mechanism. Haploids undergo morphogenetic changes like those of diploids, including the yeast–hyphal transition, chlamydospore formation and a white-opaque switch that facilitates mating. Haploid opaque cells of opposite mating type mate efficiently to regenerate the diploid form, restoring heterozygosity and fitness. Homozygous diploids arise spontaneously by auto-diploidization, and both haploids and auto-diploids show a similar reduction in fitness, in vitro and in vivo, relative to heterozygous diploids, indicating that homozygous cell types are transient in mixed populations. Finally, we constructed stable haploid strains with multiple auxotrophies that will facilitate molecular and genetic analyses of this important pathogen.

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Acknowledgements

We would like to thank M. McClellan, K. Matter, E. Voigt and F. Y. Chan for technical assistance, S. Filler and J. Becker for work involving mouse models of infection, F. M. Chang and T. Y. Ou for contributing to the isolation of the progenitor of GZY792, and L. Burrack, J. Heitman, M. Kupiec, K. Nielsen and N. Pavelka for comments on the manuscript. M.A.H. is supported by an NRSA post-doctoral fellowship (F32GM096536-02). A.F. is supported by the National Institute of Allergy and Infectious Diseases (NIAID) (R15-AI090633-01A1 and R01 AI0624273). M.P.H. is supported by a training grant for Graduate Assistance in Areas of National Need (P200A100100). B.D.H. is supported by the National Institute of Dental & Craniofacial Research (T32DE007288). R.J.B. is supported by the NIAID (AI081560 and AI081704) and a PATH Award from the Burroughs Wellcome Fund. Y.W. is supported by Agency for Science, Technology, & Research, Singapore. J.B. is supported by the NIAID (AI0624273).

Author information

Affiliations

  1. Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, Minnesota 55455, USA

    • Meleah A. Hickman
    • , Darren Abbey
    • , Benjamin D. Harrison
    •  & Judith Berman
  2. Institute of Molecular and Cell Biology, Agency for Science, Technology & Research, Singapore 138673, Singapore

    • Guisheng Zeng
    • , Yan-Ming Wang
    •  & Yue Wang
  3. Bowdoin College, Brunswick, Maine 04011, USA

    • Anja Forche
  4. Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA

    • Matthew P. Hirakawa
    •  & Richard J. Bennett
  5. Department of Microbiology and Immunology, Taipei Medical University, Taipei, Taiwan

    • Ching-hua Su
  6. Department of Molecular Microbiology and Biotechnology, George Wise Faculty of Life Sciences Tel Aviv University, Ramat Aviv, 69978 Israel

    • Judith Berman

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Contributions

M.A.H. performed flow cytometry analysis, SNP/CGH hybridizations, species identification, white-opaque switching and mating assays, and in vitro growth assays. Y.W. and G.Z. designed and analysed auxotrophs, morphogenesis mutants and in vivo growth experiments; G.Z. constructed the mutants; Y.-M.W. collected isolates post-in vivo. A.F. and C.-h.S. initially isolated haploid/homozygous isolates. D.A. developed the flow cytometry analysis and SNP/CGH pipelines. M.P.H. performed virulence and in vivo competition assays. B.D.H. collected and analysed cell and nuclear size data and budding patterns. M.A.H. and J.B. assembled the data and wrote the manuscript with editorial input from A.F., R.J.B. and Y.W.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Judith Berman.

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https://doi.org/10.1038/nature11865

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