Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans

Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections(1,2). 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 alpha cells undergo efficient cell and nuclear fusion, resulting in tetraploid a/alpha mating products(3-6). Whereas mating between a and alpha 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 alpha, typically secreted by alpha cells(7-10). C. albicans Delta bar1 a cells were shown to secrete both a and alpha mating pheromones; alpha-pheromone activated self-mating in these cells in a process dependent on Ste2, the receptor for alpha-pheromone. In addition, pheromone production by alpha 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.