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PMID: 8031026 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene.

Antimicrobial agents and chemotherapy ·Vol. 38 ·No. 4 ·1994-04-00 ·Pages 648-52

Ben-Yaacov R, Knoller S, Caldwell GA, Becker JM, Koltin Y

Abstract

Candida albicans is not inhibited by a number of drugs known to affect fungal cells. The basis for this resistance in most cases is unknown but has been attributed to the general impermeability of the fungal cell envelope. A gene (BENr) formerly shown to be responsible for the resistance of C. albicans to benomyl and methotrexate was shown in the present study to confer resistance to four other inhibitory compounds: cycloheximide, benztriazoles, 4-nitroquinoline-N-oxide, and sulfometuron methyl. Analysis of the protein database revealed an apparent similarity of the C. albicans gene to membrane protein genes encoding antibiotic resistance in prokaryotes and eukaryotes and a high degree of identity to a recently cloned gene encoding cycloheximide resistance in Candida maltosa. We propose that BENr encodes a protein that operates in a fashion similar, but not identical, to that described for other multiple-drug resistance proteins.

Related Genes
BENr PDR5 SNQ1
MeSH Terms
Amino Acid Sequence Antifungal Agents/pharmacology Base Sequence Benomyl/pharmacology Candida albicans/drug effects,genetics DNA, Fungal/metabolism Drug Resistance, Microbial/genetics Methotrexate/pharmacology Microbial Sensitivity Tests Molecular Sequence Data Plasmids Saccharomyces cerevisiae/genetics Transformation, Genetic
Chemicals
Antifungal Agents DNA, Fungal Benomyl Methotrexate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ben-Yaacov R
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Knoller S
Caldwell G A
Becker J M
Koltin Y
References (38)
38 references, click to expand
  1. A simple method for displaying the hydropathic character of a protein.
    J Mol Biol. 1982 May 5;157(1):105-32 PMID: 7108955
  2. Identification of a gene for beta-tubulin in Aspergillus nidulans.
    Cell. 1978 Oct;15(2):639-47 PMID: 363278
  3. Transformation of intact yeast cells treated with alkali cations.
    J Bacteriol. 1983 Jan;153(1):163-8 PMID: 6336730
  4. Cycloheximide resistance in yeast: the gene and its protein.
    Nucleic Acids Res. 1983 May 25;11(10):3123-35 PMID: 6304624
  5. Studies on transformation of Escherichia coli with plasmids.
    J Mol Biol. 1983 Jun 5;166(4):557-80 PMID: 6345791
  6. Cell division cycle genes nda2 and nda3 of the fission yeast Schizosaccharomyces pombe control microtubular organization and sensitivity to anti-mitotic benzimidazole compounds.
    J Mol Biol. 1983 Aug 5;168(2):271-84 PMID: 6887245
  7. Gene amplification in cultured animal cells.
    Cell. 1984 Jul;37(3):705-13 PMID: 6378386
  8. Isolation of genes from Candida albicans by complementation in Saccharomyces cerevisiae.
    Mol Gen Genet. 1985;200(3):500-2 PMID: 3900642
  9. Isolation and characterization of mutations in the beta-tubulin gene of Saccharomyces cerevisiae.
    Genetics. 1985 Dec;111(4):715-34 PMID: 2998923
  10. Mode of action of clinically important antifungal drugs.
    Adv Microb Physiol. 1986;27:1-72 PMID: 3532715
  11. Cloning and characterization of the gene for beta-tubulin from a benomyl-resistant mutant of Neurospora crassa and its use as a dominant selectable marker.
    Mol Cell Biol. 1986 Jul;6(7):2452-61 PMID: 2946938
  12. Regulation of dipeptide transport in Saccharomyces cerevisiae by micromolar amino acid concentrations.
    J Bacteriol. 1987 May;169(5):2132-6 PMID: 3553158
  13. Identification of methotrexate transport deficiency in mammalian cells using fluoresceinated methotrexate and flow cytometry.
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7154-8 PMID: 3478688
  14. Genetic characterization of hyperresistance to formaldehyde and 4-nitroquinoline-N-oxide in the yeast Saccharomyces cerevisiae.
    Mol Gen Genet. 1988 Feb;211(2):260-5 PMID: 3127660
  15. ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance.
    Mol Cell Biol. 1988 Feb;8(2):664-73 PMID: 3280970
  16. 'DNA Strider': a 'C' program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers.
    Nucleic Acids Res. 1988 Mar 11;16(5):1829-36 PMID: 2832831
  17. Hyperresistance to DNA damaging agents in yeast.
    Curr Genet. 1986;11(3):211-5 PMID: 3129200
  18. Diverse effects of beta-tubulin mutations on microtubule formation and function.
    J Cell Biol. 1988 Jun;106(6):1997-2010 PMID: 3290223
  19. Drug resistance in Candida albicans and Candida glabrata.
    Ann N Y Acad Sci. 1988;544:245-59 PMID: 3063171
  20. Yeast/E. coli shuttle vectors with multiple unique restriction sites.
    Yeast. 1986 Sep;2(3):163-7 PMID: 3333305
  21. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
  22. The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein.
    Nature. 1989 Aug 3;340(6232):400-4 PMID: 2569166
  23. Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells.
    EMBO J. 1989 Dec 20;8(13):3973-84 PMID: 2686977
  24. Molecular characterization of the two genes SNQ and SFA that confer hyperresistance to 4-nitroquinoline-N-oxide and formaldehyde in Saccharomyces cerevisiae.
    Curr Genet. 1989 Aug;16(2):65-74 PMID: 2557161
  25. Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces.
    Genetics. 1990 May;125(1):13-20 PMID: 2160400
  26. Genetic basis of multidrug resistance of tumor cells.
    J Bioenerg Biomembr. 1990 Aug;22(4):593-618 PMID: 1977744
  27. Significance of C-terminal cysteine modifications to the biological activity of the Saccharomyces cerevisiae a-factor mating pheromone.
    Mol Cell Biol. 1991 Jul;11(7):3603-12 PMID: 2046670
  28. Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate.
    Mol Gen Genet. 1991 Jun;227(2):318-29 PMID: 2062311
  29. Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene.
    Science. 1992 Apr 10;256(5054):232-4 PMID: 1348873
  30. Molecular dissection of mammalian gene amplification: new mechanistic insights revealed by analyses of very early events.
    Mutat Res. 1992 May;276(3):199-224 PMID: 1374515
  31. Cloning and sequence analysis of a Candida maltosa gene which confers resistance to cycloheximide.
    Gene. 1992 Jul 1;116(1):105-8 PMID: 1628836
  32. ABC transporters: from microorganisms to man.
    Annu Rev Cell Biol. 1992;8:67-113 PMID: 1282354
  33. Toxicity of oxalysine and oxalysine-containing peptides against Candida albicans: regulation of peptide transport by amino acids.
    J Gen Microbiol. 1992 Nov;138(11):2353-62 PMID: 1479355
  34. Topology, structure and evolution of two families of proteins involved in antibiotic and antiseptic resistance in eukaryotes and prokaryotes--an analysis.
    Gene. 1993 Feb 14;124(1):1-11 PMID: 8440470
  35. Natural cycloheximide resistance in yeast. The role of ribosomal protein L41.
    Eur J Biochem. 1993 Apr 15;213(2):841-8 PMID: 8477753
  36. Resistance of yeasts to azole-derivative antifungals.
    J Antimicrob Chemother. 1993 Apr;31(4):463-71 PMID: 8514644
  37. Studies on the pink, adenine-deficient strains of Candida albicans. I. Cultural and morphological characteristics.
    Sabouraudia. 1970 May;8(1):48-59 PMID: 5427154
  38. Physiological characterization of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and alpha factor pheromones.
    Mol Cell Biol. 1982 Jan;2(1):21-9 PMID: 7050666
Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.38.4.648
Published
1994-04-00
Pages
648-52
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC284519
Subset
IM
Grants
NIAID NIH HHS · AI 35262 · United States
NIGMS NIH HHS · GM-46250 · United States
External Links
PubMed source DOI: 10.1128/AAC.38.4.648 PMC Full Text View journal details
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