Sexual reproduction in the Candida clade: cryptic cycles, diverse mechanisms, and alternative functions

Abstract

To have sex, or not to have sex, is a question posed by many microorganisms. In favor of a sexual lifestyle is the associated rearrangement of genetic material that confers potential fitness advantages, including resistance to antimicrobial agents. The asexual lifestyle also has benefits, as it preserves complex combinations of genes that may be optimal for pathogenesis. For this reason, it was thought that several pathogenic fungi favored strictly asexual modes of reproduction. Recent approaches using genome sequencing, population analysis, and experimental techniques have now revised this simplistic picture. It is now apparent that many pathogenic fungi have retained the ability to undergo sexual reproduction, although reproduction is primarily clonal in origin. In this review, we highlight the current understanding of sexual programs in the Candida clade of species. We also examine evidence that sexual-related processes can be used for functions in addition to mating and recombination in these organisms.

Fig. 1

Mating and pathogenesis amongst members of the Candida clade. Experimental evidence refers to laboratory evidence of mating. Genomic evidence refers to the presence of genes predicted to be involved in mating from sequencing data. Population evidence refers to evidence of mating based on population structure analysis. Plus/minus indicates that the data is contradictory or inconclusive. Question marks indicate where data is lacking. The phylogenetic tree is for comparison purposes only and is not drawn to scale

Fig. 2

Heterothallic and homothallic mating in Candida albicans. A Paracrine pheromone signaling drives heterothallic mating in C. albicans. Opaque MTLα cells secrete α pheromone (MFα), which is sensed by the cell surface receptor, Ste2, on MTL a cells. Conversely, opaque MTL a cells secrete a pheromone (MFa), which is sensed by the receptor, Ste3, on MTLα cells. This inter-cellular pheromone signaling results in upregulation of mating genes, induction of polarized growth, and a-α cell fusion. B Autocrine pheromone signaling drives homothallic mating in C. albicans. It is now recognized that opaque MTL a cells secrete not only the canonical MFa pheromone but also MFα pheromone. The Bar1 aspartyl protease degrades MFα, but in the absence of this protease MFα accumulates and binds to the Ste2 receptor, resulting in auto-activation of the mating response. Subsequent same-sex conjugation of C. albicans MTL a cells occurs resulting in formation of tetraploid a cells

Fig. 3

Model for the role of Bar1 protease in white and opaque MTL a cells of C. albicans. Opaque cells exposed to pheromone highly upregulate the expression of the BAR1 gene. This upregulation results in sufficient secretion of Bar1 protease to prevent auto-activation of the mating program. However, it is predicted that in certain niches Bar1 activity is sequestered/degraded allowing for opaque cells to initiate autocrine pheromone signaling and undergo efficient same-sex mating. In contrast, when white cells are exposed to pheromone, they do not respond by upregulating expression of BAR1. It is therefore possible that the level of secreted Bar1 is insufficient to degrade exogenous α-pheromone, making these cells highly sensitive to the effects of pheromone and allowing for pheromone-enhanced biofilm formation to occur