title: Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus.
abstract: Polymerase chain reaction using degenerate primers was used to identify genes encoding proteins of the ATP-binding cassette superfamily in Aspergillus fumigatus and Aspergillus flavus. In A. fumigatus, two genes (AfuMDR1 and AfuMDR2) encoding proteins of the ATP-binding cassette superfamily were identified. One gene (AflMDR1) was isolated from A. flavus and is the apparent homologue to AfuMDR1. AfuMDR1 and AflMDR1 encode proteins of molecular weights 148,000 and 143,000, respectively, each containing 12 putative transmembrane regions and two ATP-binding sites. These proteins are arranged in two homologous halves, each half consisting of a hydrophobic region (encoding six putative transmembrane domains) and an ATP-binding site. The AfuMDR1 and AflMDR1-encoded proteins bear a high degree of similarity to the Schizosaccharomyces pombe leptomycin B resistance protein and to human MDR1. The second gene identified in A. fumigatus, AfuMDR2, encodes a protein of molecular weight 85,000, containing four putative transmembrane domains and an ATP binding domain. The encoded protein is similar to those encoded by MDL1 and MDL2, two MDR-like genes of Saccharomyces cerevisiae. Expression of AFUMDR1 in S. cerevisiae conferred increased resistance to the antifungal agent cilofungin (LY121019), an echinocandin B analog.
authors.affiliation: Department of Infectious Diseases, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Tobin
authors.forename: R B
authors.initials: RB
authors.lastname: Peery
authors.forename: P L
authors.initials: PL
authors.lastname: Skatrud
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000096:biosynthesis; D001231:Aspergillus flavus / Q000235:genetics*; D001232:Aspergillus fumigatus / Q000235:genetics*; D001419:Bacteria / Q000235:genetics; D001483:Base Sequence; D016384:Consensus Sequence; D017931:DNA Primers; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000235:genetics; D005800:Genes, Fungal; D019450:Genes, MDR; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D017931:DNA Primers; D005231:Fatty Acids, Unsaturated; C095122:multidrug resistance protein 3; C038753:leptomycin B