Abstract
Phenotypic switching allows for rapid transitions between alternative cell states and is important in pathogenic fungi for colonization and infection of different host niches. In Candida albicans, the white-opaque phenotypic switch plays a central role in regulating the program of sexual mating as well as interactions with the mammalian host. White-opaque switching is controlled by genes encoded at the MTL (mating-type-like) locus that ensures that only a or α cells can switch from the white state to the mating-competent opaque state, while a/α cells are refractory to switching. Here, we show that the related pathogen C. tropicalis undergoes white-opaque switching in all three cell types (a, α, and a/α), and thus switching is independent of MTL control. We also demonstrate that C. tropicalis white cells are themselves mating-competent, albeit at a lower efficiency than opaque cells. Transcriptional profiling of C. tropicalis white and opaque cells reveals significant overlap between switch-regulated genes in MTL homozygous and MTL heterozygous cells, although twice as many genes are white-opaque regulated in a/α cells as in a cells. In C. albicans, the transcription factor Wor1 is the master regulator of the white-opaque switch, and we show that Wor1 also regulates switching in C. tropicalis; deletion of WOR1 locks a, α, and a/α cells in the white state, while WOR1 overexpression induces these cells to adopt the opaque state. Furthermore, we show that WOR1 overexpression promotes both filamentous growth and biofilm formation in C. tropicalis, independent of the white-opaque switch. These results demonstrate an expanded role for C. tropicalis Wor1, including the regulation of processes necessary for infection of the mammalian host. We discuss these findings in light of the ancestral role of Wor1 as a transcriptional regulator of the transition between yeast form and filamentous growth.
Highlights
The incidence of opportunistic fungal infections has increased in recent years as a result of immunosuppressive diseases such as AIDS, as well as the use of immunosuppressive drugs in modern medical practices [1]
The white-opaque phenotypic switch has been extensively characterized in the human fungal pathogen Candida albicans, where it plays a central role in regulating entry into sexual reproduction
This epigenetic switch is strictly regulated by the MTL locus so that only a or a cell types can switch to the opaque state, whereas a/a cells are locked in the white state
Summary
The incidence of opportunistic fungal infections has increased in recent years as a result of immunosuppressive diseases such as AIDS, as well as the use of immunosuppressive drugs in modern medical practices [1]. Candida species are typically harmless commensals of humans but are important fungal pathogens, responsible for both systemic and mucosal opportunistic infections [2]. Three Candida clade pathogens, Candida albicans, Candida dubliniensis, and Candida tropicalis, have been shown to undergo an epigenetic switch between distinct ‘white’ and ‘opaque’ states [5,6,7,8], and this phenotypic switch plays a crucial role in modulating behavior. While C. albicans represents the most commonly isolated Candida species in the clinic, C. dubliniensis is rarely found in infections, which may reflect the more limited ability of this species to undergo filamentation [2,19]. Relatively little is known about the biology of C. tropicalis compared to that of the model species C. albicans, including the factors that promote pathogenesis in the mammalian host
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