N-Acetylglucosamine Induces White-to-Opaque Switching and Mating in Candida tropicalis, Providing New Insights into Adaptation and Fungal Sexual Evolution

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Eukaryotic Cell (Impact Factor: 3.18). 04/2012; 11(6):773-82. DOI: 10.1128/EC.00047-12
Source: PubMed


Pathogenic fungi are capable of switching between different phenotypes, each of which has a different biological advantage. In the most prevalent human fungal pathogen, Candida albicans, phenotypic transitions not only improve its adaptation to a continuously changing host microenvironment but also regulate sexual mating. In this report, we show that Candida tropicalis, another important human opportunistic pathogen, undergoes reversible and heritable phenotypic switching, referred to as the "white-opaque" transition. Here we show that N-acetylglucosamine (GlcNAc), an inducer of white-to-opaque switching in C. albicans, promotes opaque-cell formation and mating and also inhibits filamentation in a number of natural C. tropicalis strains. Our results suggest that host chemical signals may facilitate this phenotypic switching and mating of C. tropicalis, which had been previously thought to reproduce asexually. Overexpression of the C. tropicalis WOR1 gene in C. albicans induces opaque-cell formation. Additionally, an intermediate phase between white and opaque was observed in C. tropicalis, indicating that the switching could be tristable.

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    • "Miller and Johnson (23) also demonstrated that a switch from white to opaque was necessary for mating and this was again found to be a general rule for most natural strains by Lockhart et al. (28, 29). The white–opaque switch, therefore, represented a unique phenotypic transition inserted as a step in the mating program of C. albicans and the related species Candida dubliniensis (30) and Candida tropicalis (31–33). A similar transition was not a requirement for mating amongst members of the Saccharomyces clade of the hemiascomycetes, which includes Saccharomyces cerevisiae and the pathogen Candida glabrata. "
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    ABSTRACT: The "white-opaque" transition in Candida albicans was discovered in 1987. For the next fifteen years, a significant body of knowledge accumulated that included differences between the cell types in gene expression, cellular architecture and virulence in cutaneous and systemic mouse models. However, it was not until 2002 that we began to understand the role of switching in the life history of this pathogen, the role of the mating type locus and the molecular pathways that regulated it. Then in 2006, both the master switch locus WORI and the pheromone-induced white cell biofilm were discovered. Since that year, a number of new observations on the regulation and biology of switching have been made that have significantly increased the perceived complexity of this fascinating phenotypic transition.
    Journal of Oral Microbiology 01/2014; 6(1). DOI:10.3402/jom.v6.22993
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    ABSTRACT: Signal transduction pathways regulating growth and stress responses are areas of significant study in the effort to delineate pathogenic mechanisms of fungi. In-depth knowledge of signal transduction events deepens our understanding of how a fungal pathogen is able to sense changes in the environment and respond accordingly by modulation of gene expression and re-organization of cellular activities to optimize fitness. Members of the Ras protein family are important regulators of growth and differentiation in eukaryotic organisms, and have been the focus of numerous studies exploring fungal pathogenesis. Here, the current data regarding Ras signal transduction are reviewed for three major pathogenic fungi: Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. Particular emphasis is placed on Ras-protein interactions during control of morphogenesis, stress response and virulence.
    01/2012; 2(1):105. DOI:10.4172/2165-8056.1000105
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    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.
    PLoS Genetics 03/2013; 9(3):e1003369. DOI:10.1371/journal.pgen.1003369 · 7.53 Impact Factor
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