THE CANDIDA-ALBICANS HYR1 GENE, WHICH IS ACTIVATED IN RESPONSE TO HYPHAL DEVELOPMENT - BELONGS TO A GENE FAMILY ENCODING YEAST-CELL WALL PROTEINS

A hyphally regulated gene (HYR1) from the dimorphic human pathogenic f ungus Candida albicans was isolated and characterized. Northern (RNA) analyses showed that the HYR1 mRNA was induced specifically in respons e to hyphal development when morphogenesis was stimulated by serum add ition and temperature elevation, increases in both culture pH and temp erature, or N-acetylglucosamine addition. The HYR1 gene sequence revea led a 937-codon open reading frame capable of encoding a protein with an N-terminal signal sequence, a C-terminal glycosylphosphatidylinosit ol-anchoring domain, 17 potential N glycosylation sites, and a large d omain rich in serine and threonine (51% of 230 residues). These featur es are observed in many yeast cell wall proteins, but no homologs are present in the databases. In addition, Hyr1p contained a second domain rich in glycine, serine, and asparagine (79% of 239 residues), The HY R1 locus in C. albicans CAI4 was disrupted by ''Ura-blasting,'' but th e resulting homozygous Delta hyr1/Delta hyr1 null mutant displayed no obvious morphological phenotype. The growth rates for yeast cells and hyphae and the kinetics of germ tube formation in the null mutant were unaffected. Aberrant expression of HYR1 in yeast cells, when an ADH1- HYR1 fusion was used, did not stimulate hyphal formation in C. albican s or pseudohyphal growth in Saccharomyces cerevisiae, HYR1 appears to encode a nonessential component of the hyphal cell wall.