Investigation
of the potential role of Ace2p as a virulence factor in Candida albicans.
Mary. T Kelly (1),
Frank Odds (2), Geraldine Butler (1)
(1) Dept. of Biochemistry, DMMC University College Dublin, Merville House,
Belfield, Dublin, 04, Ireland (Mary.T.Kelly@ucd.ie); (2) Dept. of Molecular and
Cell Biology, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD,
Scotland, United Kingdom
Candida albicans can cause a range of infections from superficial thrush to Candida septicemia. The Pathogenicity of C. albicans is attributed mainly to its ability to undergo a morphogenetic switch, from unicellular yeast to a filamentous, hyphal form with increased virulence. One of a number changes within the cell wall during this switch is an increase in chitin levels. While C. albicans is known to contain 3 chitin synthase enzymes and 3 chtinase enzymes, little is known about the regulation of these genes at the transcriptional level. In Saccharomyces cerevisiae, where extensive work has been done, Ace2p is known to regulate the expression of the single chitinase gene in this yeast and deletion of Ace2p causes a pseudohyphal morphology and reduced adhesion to solid agar. We have identified a single homologue of Ace2p, CaAce2p, in the partially completed C. albicans genome sequence. Deletion of CaAce2p causes flocculation in liquid media due to clumping of the cells, raised colonies on solid agar, and an increased tendency to form pseudohyphae under non-hyphal-inducing conditions. Using murine models, we have established that deletion of CaAce2p also reduces the virulence of this normally pathogenic organism. Here we report on analysis of the levels of expression of the three chitinase genes, biofilm formation as an indication of the adhesion properties of the ace2/ace2 strains, and the changes in cellular morphology caused by the deletion of CaAce2p.