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Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans.

ABSTRACT: Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections. 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. 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. C. albicans Deltabar1 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.

SUBMITTER: Alby K

PROVIDER: S-EPMC2866515 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans.

Alby Kevin K Schaefer Dana D Bennett Richard J RJ

Nature 20090801 7257

Candida albicans is the most common fungal pathogen in humans, causing both debilitating mucosal infections and potentially life-threatening systemic infections. 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. Whereas mating between a and alpha cells has been established ...[more]

PMID: 19675652

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Project description:UNLABELLED:It has been proposed that the ancestral fungus was mating competent and homothallic. However, many mating-competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating, the essentially obligate diploid ascomycete pathogen Candida albicans has to change its mating type locus from heterozygous MTLa/? to homozygous MTLa/a or MTL?/? and then undergo an environmentally controlled epigenetic switch to the mating-competent opaque form. These requirements greatly reduce the potential for C. albicans mating. Deletion of the Yci1 domain gene OFR1 bypasses the need for C. albicans cells to change the mating type locus from heterozygous to homozygous prior to switching to the opaque form and mating and allows homothallic mating of MTL heterozygous strains. This bypass is carbon source dependent and does not occur when cells are grown on glucose. Transcriptional profiling of ofr1 mutant cells shows that in addition to regulating cell type and mating circuitry, Ofr1 is needed for proper regulation of histone and chitin biosynthesis gene expression. It appears that OFR1 is a key regulator in C. albicans and functions in part to maintain the cryptic mating phenotype of the pathogen. IMPORTANCE:Candida albicans is a human fungal pathogen with a recently discovered, highly cryptic mating ability. For efficient mating, it has to lose heterozygosity at its mating type locus. Then, MTL homozygous strains can undergo an epigenetic switch to an elongated yeast state, termed the opaque form, and become mating competent. This infrequent two-step process greatly reduces the potential for mating; few strains are MTL homozygous, and the opaque state is unstable at the temperature of the mammalian host. C. albicans has a complex mechanism for mating that appears designed to ensure that mating is infrequent. Here, we have characterized a new gene, opaque-formation regulator 1 (OFR1). Deleting the OFR1 gene allows MTL A: /? strains to mate efficiently with either mating type or even mate homothallically. It is possible that downregulating OFR1 in the host environment could allow mating in C. albicans by a route that does not involve MTL homozygosis.

Project description:BACKGROUND:Opportunistic yeast pathogens of the genus Candida are an important medical problem. Candida albicans, the most prevalent Candida species, is a natural commensal of humans that can adopt a pathogenic behavior. This species is highly heterozygous and cannot undergo meiosis, adopting instead a parasexual cycle that increases genetic variability and potentially leads to advantages under stress conditions. However, the origin of C. albicans heterozygosity is unknown, and we hypothesize that it could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. RESULTS:Our results show compelling evidence that C. albicans is an evolved hybrid. The genomic patterns observed in C. albicans are similar to those of other hybrids such as Candida orthopsilosis MCO456 and Candida inconspicua, suggesting that it also descends from a hybrid of two divergent lineages. Our analysis indicates that most of the divergence between haplotypes in C. albicans heterozygous blocks was already present in a putative heterozygous ancestor, with an estimated 2.8% divergence between homeologous chromosomes. The levels and patterns of ancestral heterozygosity found cannot be fully explained under the paradigm of vertical evolution and are not consistent with continuous gene flux arising from lineage-specific events of admixture. CONCLUSIONS:Although the inferred level of sequence divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor and diverged by extensive loss of heterozygosity. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

Dataset Information

Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans.

Publications

Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans.

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