Posters: Analysis of sterol regulation in the Saccharomycotina.

POSTERS Analysis of sterol regulation in the Saccharomycotina. Many fungal pathogens grow on superficial and in internal sites in infected hosts, regions that have considerably different oxygen levels. A better understanding of the influence of hypoxia (low oxygen) on virulence and pathogenesis may lead to improved treatments against systemic fungal infections. Hypoxia induces filamentation of Candida albicans, which is associated with virulence. However other pathogenic Candida species do not grow as filaments, and presumably respond to hypoxia in different ways. In many fungal species (including the Saccharomyces and Candida clades) the transcription factor Upc2 plays a major role in regulating expression of the sterol pathway, particularly in low oxygen conditions. In other fungi, such as fission yeast Schizosaccharomyces pombe and the human pathogens Aspergillus fumigatus and Cryptococcus neoformans, expression of sterol genes is regulated by SREBP (Sterol Regulatory Element Binding Protein). SREPB is an ancient regulator that is conserved in mammals (including humans). The genome of Yarrowia lipolytica, an out-group of Saccharomyces and Candida clade species, contains homologues of both Upc2 and SREBP. By carrying out gene deletions in this species, we have shown that the appearance of Upc2 coincides with the acquisition of sterol pathway regulation. Our results also suggest that the remnants of the SREBP proteins regulate morphology and filamentous growth. Efg1 regulates morphology and biofilm formation in Candida parapsilosis. The incidence of infection by Candida parapsilosis has risen substantially in recent years, possibly because it is easily transmitted to patients from contaminated external sources such as medical devices, catheters, or the hands of health care workers. One of the known virulence factors of C. parapsilosis is its ability to form biofilms on indwelling medical devices. In the related species Candida albicans, the transcription factor EFG1 is a major regulator of biofilm development and hyphal growth (Ramage et al., 2002). Efg1 is also an important regulator of white-to-opaque switching (Zordan et al., 2007) The role of EFG1 in Candida parapsilosis has not yet been studied in detail. Here we show that in contrast to C. albicans the Efg1 ortholog in Candida parapsilosis is a major regulator of a morphological switch at the colony level, from wrinkled to smooth phenotypes. The rate of switching is greatly increased in an efg1 knockout. The phenotypes of the two colony types are significantly different, suggesting that that there are differences in the cell walls. Smooth cells with an efg1 deletion are more …