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

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fungi from the genus Candida are common members of the human microbiota; however, they are also important opportunistic pathogens in immunocompromised hosts. Several morphological transitions have been linked to the ability of these fungi to occupy the different ecological niches in the human body. The transcription factor Efg1 from the APSES family plays a central role in the transcription circuits underlying several of these morphological changes. In Candida albicans, for example, Efg1 is a central regulator of filamentation, biofilm formation and white-opaque switching, processes associated with survival in the human host. Orthologs of Efg1 are present throughout the Candida clade but, surprisingly, the genome sequence of Candida tropicalis failed to uncover a gene coding for Efg1. One possibility was that the paralog of Efg1, Efh1, had assumed the function of Efg1 in C. tropicalis. However, we show that this gene has only a minor role in the morphological transitions mentioned above. Instead, we report here that C. tropicalis does contain an ortholog of the EFG1 gene found in other Candida species. The gene is located in a different genomic position than EFG1 in C. albicans, in a region that contains a gap in the current genome assembly of C. tropicalis. We show that the newly identified C. tropicalis EFG1 gene regulates filamentation, biofilm formation and white-opaque switching. Our results highlight the conserved role of Efg1 in controlling morphogenesis in Candida species, and remind us that published genome sequences are drafts that require continuous curation and careful scrutiny. Copyright © 2015 Author et al.
    G3-Genes Genomes Genetics 03/2015; 5(5). DOI:10.1534/g3.115.017566 · 2.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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. DOI:10.3402/jom.v6.22993
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human fungal pathogens can exist in a variety of ploidy states, including euploid and aneuploid forms. Ploidy change has a major impact on phenotypic properties, including the regulation of interactions with the human host. In addition, the rapid emergence of drug-resistant isolates is often associated with the formation of specific supernumerary chromosomes. Pathogens such as Candida albicans and Cryptococcus neoformans appear particularly well adapted for propagation in multiple ploidy states with novel pathways driving ploidy variation. In both species, heterozygous cells also readily undergo loss of heterozygosity (LOH), leading to additional phenotypic changes such as altered drug resistance. Here, we examine the sexual and parasexual cycles that drive ploidy variation in human fungal pathogens and discuss ploidy and LOH events with respect to their far-reaching roles in fungal adaptation and pathogenesis.
    Cold Spring Harbor Perspectives in Medicine 07/2014; 4(10). DOI:10.1101/cshperspect.a019604 · 7.56 Impact Factor