Functional analysis of the vacuole in Candida albicans

The fungal vacuole is an acidic membrane bound compartment, containing a range of hydrolytic enzymes. Its functions include recycling of cellular proteins through degradation, storage of cellular metabolites, and homeostasis of the cytoplasmic environment. In the model eukaryote Saccharomyces cerevisiae, vacuolar function is non-essential for vegetative growth, since mutant strains deficient for vacuole function are viable. However, vacuolar function appears to be more important for survival under conditions of nutritional, osmotic, and temperature stress. Furthermore, mutants deficient in vacuolar hydrolase activity are unable to sporulate. This suggests that the vacuole plays an important role during processes of adaptation and differentiation. The vacuole has been well characterised in the model fungi S. cerevisiae, and Aspergillus nidulans, but to date little is known about the functions of the vacuole in the human fungal pathogen Candida albicans. It has been postulated that the vacuole is likely to play a central role in the adaptation of C. albicans to host environments during the process of infection. Moreover, the vacuole has previously been observed to undergo rapid expansion during the emergence of a germ-tube from a yeast cell, to occupy the majority of the parent yeast cell. This process of the yeast-hyphal switch has been implicated in virulence. The class-C vps mutants of S. cerevisiae are defective in vacuole biogenesis and lack a vacuolar compartment. In this study C. albicans homologues of the S. cerevisiae class-C VPS genes, have been identified. Consistent with a role in vacuole enlargement during the yeast-hyphae switch, transcription of a VPS18 like ORF (CaVPS18) was found to be increased during the process of germ-tube formation. Disruption of a C. albicans VPS11 homologue (CaVPSll), resulted in a number of phenotypes similar to that of the class-C vps mutants of S. cerevisiae. Furthermore, a cavpsll null strain was delayed in the emergence of germ-tubes upon serum induction of filamentous growth, and had a reduced apical extension rate compared to its parental strain. These results support a model whereby vacuole enlargement is necessary to support the rapid emergence and extension of the germ-tube from the parent yeast cell. Further analysis of vacuolar function in C. albicans should elucidate some of the processes underlying the yeast-hypha switch.