Project description:Modes of sexual reproduction in eukaryotic organisms are highly diversified. The human fungal pathogen Candida albicans undergoes a phenotypic switch from the white to the opaque phase in order to become mating-competent. In this study, we report that functionally and morphologically differentiated white and opaque cells show a coordinating behavior in the process of mating. Although white cells are mating-incompetent, they are induced to produce sexual pheromones when treated with opposite pheromones or interacted with opaque cells of an opposite mating type. In a co-culture system, pheromones released by white cells induce opaque cells to form mating projections and thus facilitate both opposite- and same-sex mating of opaque cells. Deletion of genes encoding the pheromone precursor proteins and inactivation of the pheromone response signaling pathway (Ste2-MAPK-Cph1) impair the promoting role of white cells (MTLa) in sexual mating of opaque cells. White and opaque cells communicate via a paracrine pheromone signaling and thus create an environment conducive to sexual mating. This coordination behavior of the two different cell types may be a trade-off strategy between sexual and asexual lifestyles in C. albicans.
Project description:Modes of sexual reproduction in eukaryotic organisms are highly diversified. The human fungal pathogen Candida albicans undergoes a phenotypic switch from the white to the opaque phase in order to become mating-competent. In this study, we report that functionally and morphologically differentiated white and opaque cells show a coordinating behavior in the process of mating. Although white cells are mating-incompetent, they are induced to produce sexual pheromones when treated with opposite pheromones or interacted with opaque cells of an opposite mating type. In a co-culture system, pheromones released by white cells induce opaque cells to form mating projections and thus facilitate both opposite- and same-sex mating of opaque cells. Deletion of genes encoding the pheromone precursor proteins and inactivation of the pheromone response signaling pathway (Ste2-MAPK-Cph1) impair the promoting role of white cells (MTLa) in sexual mating of opaque cells. White and opaque cells communicate via a paracrine pheromone signaling and thus create an environment conducive to sexual mating. This coordination behavior of the two different cell types may be a trade-off strategy between sexual and asexual lifestyles in C. albicans. total RNA profiles of white cell treated with pheromone
Project description:The human fungal pathogen Candida albicans can switch stochastically and heritably between a “white” phase and an “opaque” phase. Opaque cells are the mating-competent form of the species whereas white cells are essentially “sterile”. Here, we report that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating. The relative expression levels of pheromone-sensing and mating-associated genes (including STE2/3, MFA1, MFalpha1, FIG1, FUS1, and CEK1/2) were increased under glucose depletion conditions, while expression of mating repressors TEC1 and DIG1 was decreased. We show that Cph1 and Tec1, factors that act downstream of the pheromone MAPK pathway, play opposite roles in regulating white cell mating as TEC1 deletion or CPH1 overexpression promoted white cell mating. Moreover, inactivation of the Cph1 repressor Dig1 increased white cell mating ~4,000 fold in glucose-depleted medium relative to that in the presence of glucose. These findings reveal that the white-to-opaque epigenetic switch may not be a prerequisite for sexual mating in C. albicans in nature. Given parallels between C. albicans white cell mating to that of other yeast species, this mechanism of mating could represent a more ancient strategy of sexual reproduction in C. albicans.
Project description:As a successful commensal and pathogen of humans, Candida albicans encounters a wide range of environmental changes. Among them, ambient pH is an important factor, which changes frequently and affects many biological processes in this species. The ability to adapt to pH changes is tightly linked with pathogenesis and morphogenesis. In this study, we report that pH has a profound effect on white-opaque switching and sexual mating in C. albicans. Acidic pHs promote white-to-opaque switching but repress sexual mating of opaque cells. The cAMP signaling and Rim101-mediated pH sensing pathways are involved in the regulation of pH-regulated white-opaque switching. Interestingly, white and opaque cells of the cyr1/cyr1 mutant, which is defective in producing cAMP, show distinct growth defects under acidic and alkaline conditions. Phr2 could play a major role in acidic pHs-induced opaque cell formation. We further discover that acidic pH conditions repress sexual mating due to the failure of activation of the Ste2-mediated a-pheromone response pathway. The effects of pH changes on phenotypic switching and sexual mating could be a balance behavior between host adaptation and sexual reproduction.
Project description: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 C. albicans has to homozygose its mating type locus from MTLa/α to MTLa/a or MTLα/α, 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 YciI domain gene OFR1 bypasses the need for C. albicans cells to homozygose the mating type locus 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. Distruption of OFR1 gene which encodes a Yci1 related domain in Candida ablicans (MTLa/α) is shown to have white-opaque switching related and mating related gene expression. The expression of histone genes are also positively regulated in some conditions.
Project description:In this study, we report that glucose starvation and oxidative stress, common environmental stresses encountered by the pathogen, induce the development of mating projections and efficiently permit same-sex mating in C. albicans with an “a” mating type (MTLa/a).