Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections1,2. Until recently, C. albicans was thought to be strictly asexual, existing only as an obligate diploid. A cryptic mating cycle has since been uncovered in which diploid a and α cells undergo efficient cell and nuclear fusion, resulting in tetraploid a/α mating products3,4,5,6. Whereas mating between a and α cells has been established (heterothallism), we report here two pathways for same-sex mating (homothallism) in C. albicans. First, unisexual populations of a cells were found to undergo autocrine pheromone signalling and same-sex mating in the absence of the Bar1 protease. In both C. albicans and Saccharomyces cerevisiae, Bar1 is produced by a cells and inactivates mating pheromone α, typically secreted by α cells7,8,9,10. C. albicans Δbar1 a cells were shown to secrete both a and α mating pheromones; α-pheromone activated self-mating in these cells in a process dependent on Ste2, the receptor for α-pheromone. In addition, pheromone production by α cells was found to promote same-sex mating between wild-type a cells. These results establish that homothallic mating can occur in C. albicans, revealing the potential for genetic exchange even within unisexual populations of the organism. Furthermore, Bar1 protease has an unexpected but pivotal role in determining whether sexual reproduction can potentially be homothallic or is exclusively heterothallic. These findings also have implications for the mode of sexual reproduction in related species that propagate unisexually, and indicate a role for specialized sexual cycles in the survival and adaptation of pathogenic fungi.
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The authors would like to thank D. MacCallum and the Aberdeen Fungal Group for strains, and J. Laney, T. Serio, R. Sherwood and M. Tessmer for discussions and critical reading of the manuscript. We also thank D. Koveal and S. Gilman for assistance during the preliminary stages of this work. R.J.B. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. K.A. was supported by a training grant for Graduate Assistance in Areas of National Need.
Author Contributions K.A. constructed mutant strains, analysed mating phenotypes, quantified mating frequencies and performed biofilm assays. D.S. constructed mutant strains, quantified mating frequencies and performed biofilm and halo assays. R.J.B. constructed mutant strains, quantified mating frequencies, performed adherence assays and analysed mating zygotes. K.A. and R.J.B. were involved in study design and writing of the manuscript.
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Alby, K., Schaefer, D. & Bennett, R. Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature 460, 890–893 (2009) doi:10.1038/nature08252
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