Abstract 938 Infectious Diseases Platform, Tuesday, 5/4

The product of the Candida albicans gene INT1 functions in adhesion to epithelial cells, morphologic switching to filamentous forms and virulence of the organism(1). The function of Int1p in both adhesion and morphogenesis fits the paradigm of the vertebrate integrins. Int1p expression in the model yeast Saccharomyces cerevisiae causes a morphology change: buds hyperpolarize to form long filaments(2). The filamentous phenotype caused by Int1p expression is similar to that seen in S. cerevisiae septin mutant strains. Septins are cytoskeletal-associated proteins that form the ring structure at the mother-bud neck that is required for cytokines. In both Int1p-expressing and cdc12 septin-mutant strains, chitin is delocalized and cytokinesis is defective. We are using green fluorescent protein (Gfp)-tagged genetic constructs to study the in vivo localization of Int1p and septins in S. cerevisiae. Int1p expression in S. cerevisiae causes a striking new localization pattern of at least two septins, Sep7p and Cdc3p, that is very different from the diffuse cytoplasmic localization seen in a cdc12 mutant cell. In Int1p-expressing cells, these septins form an elaborate spiral structure at the cell periphery that suggests a specific alteration in the assembly of the septin ring. The localization of septins in Int1p-expressing cells is also different than that seen in a cla4 clb1 clb3 clb4 strain that has a similar elongated bud phenotype(3). Intriguingly, Int1p also localizes in an elaborate spiral pattern similar to that of the septins. These data implicate an interaction between Int1p and cytoskeletal proteins in S. cerevisiae, providing another similarity between Int1p and vertebrate integrins and insight into how Int1p may be effecting morphogenesis in C. albicans. Immunofluorescence co-localization experiments and yeast two-hybrid studies are currently in progress to further evaluate the interaction between Int1p and septins in S. cerevisiae. The effect of Int1p on the localization of C. albicans septin homologs is also underway.