Candida albicans is part of the normal human microflora colonizing the mouth, skin, gastrointestinal and respiratory tract of 70% of healthy individuals. However, overgrowth can cause local infection and life threatening systemic candidemia, especially in immunocompromised people (Ruhnke and Maschmeyer, 2002). In the USA, candidemia is the fourth most common cause of serious nosocomial infections causing approximately 10,000 deaths each year (Sudberry et al., 2004). Yet, despite the significant rate of mortality, key aspects of C. albicans' sexual life cycle have remained elusive. Sexually dimorphic a and ? cells mate both in vitro and in vivo in a mammalian host, producing tetraploid a/? cells (Hull et al., 2000; Magee and Magee, 2000). In most sexually reproducing organisms, completion of the mating cycle occurs by meiosis, effectively halving the DNA content in the cell. In C. albicans, however, no experimental conditions have been identified capable of inducing meiotic division. Instead, an alternative type of reductional division has been observed in the laboratory, in which growth of tetraploids on certain media results in random chromosome loss and resultant diploid formation by means of a parasexual cycle (Bennett and Johnson, 2003). It is still a possibility that a cryptic meiosis remains to be discovered in C. albicans, particularly given the fact that the sequenced C. albicans genome contains homologs of many genes that act specifically in meiosis in the model yeast Saccharomyces cerevisiae (Tzung et al., 2001; Bennett and Johnson, 2005).
The first aim of this proposal will therefore use a genetics based approach to identify factors capable of inducing meiosis in C. albicans.
The second aim of the proposal will use an independent method for studying meiosis in C. albicans. It has recently been shown that Candida lusitaniae, a closely related yeast to C. albicans, has a complete sexual mating cycle (Young et al., 2000, Francois et al., 2001). C. lusitaniae a and ? haploid cells mate to form diploid cells that immediately undergo meiosis in nutrient poor conditions. In parallel with the first aim, I propose to use meiosis in C. lusitaniae as a tool to investigate 'meiosis- specific' genes from C. albicans. In particular, I propose to see if C. albicans genes are capable of complementing for their homologues during meiosis in C. lusitaniae. PUBLIC HEALTH RELEVENCE: These studies are relevant as the lack of a sexual mating cycle has significantly hindered studies of C. albicans and the establishment of a meiotic pathway will open up the study of this organism to classical yeast genetic approaches. ? ? ?
| Sherwood, Racquel Kim; Scaduto, Christine M; Torres, Sandra E et al. (2014) Convergent evolution of a fused sexual cycle promotes the haploid lifestyle. Nature 506:387-390 |
| Alby, Kevin; Schaefer, Dana; Sherwood, Racquel Kim et al. (2010) Identification of a cell death pathway in Candida albicans during the response to pheromone. Eukaryot Cell 9:1690-701 |
| Sherwood, Racquel K; Bennett, Richard J (2009) Fungal meiosis and parasexual reproduction--lessons from pathogenic yeast. Curr Opin Microbiol 12:599-607 |
