title: The AUR1 gene in Saccharomyces cerevisiae encodes dominant resistance to the antifungal agent aureobasidin A (LY295337).
abstract: Aureobasidin A (LY295337) is a cyclic depsipeptide antifungal agent with activity against Candida spp. The mechanism of action of LY295337 remains unknown. LY295337 also shows activity against the yeast Saccharomyces cerevisiae. Generation of a mutant of S. cerevisiae resistant to LY295337 is reported. Resistance was found to reside in a dominant mutation of a single gene which has been named AUR1 (aureobasidin resistance). This gene was cloned and sequenced. A search for homologous sequences in GenBank and by BLAST did not elucidate the function of this gene, although sequence homology too an open reading frame from the Saccharomyces genome sequencing project and several other adjacent loci was noted. Deletion of aur1 was accomplished in a diploid S. cerevisiae strain. Subsequent sporulation and dissection of the aur1/aur1 delta diploid resulted in tetrads demonstrating 2:2 segregation of viable and nonviable spores, indicating that deletion of aur1 is lethal. As LY295337 is fungicidal and deletion of aur1 is lethal, aur1 represents a potential candidate for the target of LY295337.
authors.affiliation: Department of Infectious Disease Research, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46285, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Heidler
authors.forename: J A
authors.initials: JA
authors.lastname: Radding
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001483:Base Sequence; D001931:Brain Mapping; D003001:Cloning, Molecular; D003470:Culture Media; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics*; D006602:Hexosyltransferases; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003470:Culture Media; D005656:Fungal Proteins; D010455:Peptides; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase; C096018:LY 295337