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PMID: 8494372 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The 3' conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants.

Antimicrobial agents and chemotherapy ·Vol. 37 ·No. 4 ·1993-04-00 ·Pages 761-8

Paulsen IT, Littlejohn TG, Rådström P, Sundström L, Sköld O, Swedberg G, Skurray RA

Abstract

Nucleotide sequence analysis of ORF1 from the integron on the broad-host-range plasmid R751 revealed that the first 94 of 110 codons of ORF1 from R751 are identical to ORF4, an open reading frame from the 3' conserved segment of other integrons found in gram-negative bacteria, after which point they diverged completely. The predicted products of both ORF1 and ORF4 share homology with the multidrug exporter QacC. Phenotypic analysis revealed that ORF1 specifies a resistance profile to antiseptics and disinfectants almost identical to that of qacC, whereas ORF4 specifies much lower levels of resistance to these compounds. ORF4, whose product lacks the C-terminal 16 amino acids of the ORF1 protein, may have evolved by the interruption of ORF1 from the insertion of a DNA segment carrying a sulI sulfonamide resistance determinant. Hence, ORF1 was designated qacE, and its partially functional deletion derivative, ORF4, was designated qacE delta 1. Fluorimetric experiments indicated that the mechanism of resistance mediated by QacE, the protein specified by qacE, is active export energized by proton motive force. Amino acid sequence comparisons revealed that QacE is related to a family of small multidrug export proteins with four transmembrane segments.

Related Genes
ORF1 ORF4 qacC qacEi qace&dgr 1
MeSH Terms
Amino Acid Sequence Anti-Infective Agents, Local/pharmacology Base Sequence DNA, Recombinant Disinfectants/pharmacology Drug Resistance, Microbial/genetics Escherichia coli/genetics Ethidium/chemistry Genes, Bacterial Klebsiella pneumoniae/drug effects,genetics Molecular Sequence Data Open Reading Frames Sequence Homology, Amino Acid
Chemicals
Anti-Infective Agents, Local DNA, Recombinant Disinfectants Ethidium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Paulsen I T
School of Biological Sciences, University of Sydney, New South Wales, Australia.
Littlejohn T G
Rådström P
Sundström L
Sköld O
Swedberg G
Skurray R A
References (57)
57 references, click to expand
  1. Isolation of tobacco DNA segments with plant promoter activity.
    Mol Cell Biol. 1986 Dec;6(12):4486-92 PMID: 3540612
  2. A leptomycin B resistance gene of Schizosaccharomyces pombe encodes a protein similar to the mammalian P-glycoproteins.
    Mol Microbiol. 1992 Mar;6(6):761-9 PMID: 1349418
  3. Novel type of plasmid-borne resistance to trimethoprim.
    Antimicrob Agents Chemother. 1987 Jan;31(1):60-6 PMID: 3566240
  4. The phosphonium ion efflux system of Escherichia coli: relationship to the ethidium efflux system and energetic studies.
    J Gen Microbiol. 1986 Nov;132(11):3187-93 PMID: 3305782
  5. Nucleotide sequence and comparative analysis of the frd operon encoding the fumarate reductase of Proteus vulgaris. Extensive sequence divergence of the membrane anchors and absence of an frd-linked ampC cephalosporinase gene.
    Eur J Biochem. 1987 Sep 15;167(3):481-8 PMID: 3308458
  6. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7378-82 PMID: 2823258
  7. Homology of ORFs from Tn2603 and from R46 to site-specific recombinases.
    Nucleic Acids Res. 1987 Dec 10;15(23):10055 PMID: 2827107
  8. Transposon Tn21 encodes a RecA-independent site-specific integration system.
    Mol Gen Genet. 1988 Feb;211(2):320-5 PMID: 2832705
  9. Effects of indole alkaloids on multidrug resistance and labeling of P-glycoprotein by a photoaffinity analog of vinblastine.
    Biochem Biophys Res Commun. 1988 Jun 30;153(3):959-66 PMID: 2898941
  10. Site-specific recombination promotes linkage between trimethoprim- and sulfonamide resistance genes. Sequence characterization of dhfrV and sulI and a recombination active locus of Tn21.
    Mol Gen Genet. 1988 Aug;213(2-3):191-201 PMID: 3054482
  11. Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum.
    Cell. 1989 Jun 16;57(6):921-30 PMID: 2701941
  12. The biochemistry of P-glycoprotein-mediated multidrug resistance.
    Annu Rev Biochem. 1989;58:137-71 PMID: 2570548
  13. Physical and biochemical characterization of the qacA gene encoding antiseptic and disinfectant resistance in Staphylococcus aureus.
    J Gen Microbiol. 1989 Jan;135(1):1-10 PMID: 2778425
  14. Nucleotide sequence of a gene that encodes resistance to ethidium bromide from a transferable plasmid in Staphylococcus aureus.
    Nucleic Acids Res. 1989 Dec 11;17(23):10103 PMID: 2602117
  15. Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4781-5 PMID: 1675788
  16. Structure and evolution of a family of genes encoding antiseptic and disinfectant resistance in Staphylococcus aureus.
    Gene. 1991 May 15;101(1):59-66 PMID: 1840534
  17. Nucleotide sequence of the ethidium efflux gene from Escherichia coli.
    FEMS Microbiol Lett. 1991 Aug 1;66(2):229-31 PMID: 1936950
  18. The multidrug efflux transporter of Bacillus subtilis is a structural and functional homolog of the Staphylococcus NorA protein.
    Antimicrob Agents Chemother. 1992 Feb;36(2):484-5 PMID: 1605617
  19. A staphylococcal multidrug resistance gene product is a member of a new protein family.
    Plasmid. 1992 Mar;27(2):119-29 PMID: 1615062
  20. Cloning and characterization of the mvrC gene of Escherichia coli K-12 which confers resistance against methyl viologen toxicity.
    Nucleic Acids Res. 1992 Jun 25;20(12):3159-65 PMID: 1320256
  21. PROFILEGRAPH: an interactive graphical tool for protein sequence analysis.
    Comput Appl Biosci. 1992 Aug;8(4):331-7 PMID: 1498688
  22. Substrate specificity and energetics of antiseptic and disinfectant resistance in Staphylococcus aureus.
    FEMS Microbiol Lett. 1992 Aug 15;74(2-3):259-65 PMID: 1526458
  23. Membrane transport proteins: implications of sequence comparisons.
    Curr Opin Cell Biol. 1992 Aug;4(4):684-95 PMID: 1419050
  24. The integron In1 in plasmid R46 includes two copies of the oxa2 gene cassette.
    Plasmid. 1992 Nov;28(3):225-34 PMID: 1334268
  25. Nucleotide sequence of the AAD(2'') aminoglycoside adenylyltransferase determinant aadB. Evolutionary relationship of this region with those surrounding aadA in R538-1 and dhfrII in R388.
    Nucleic Acids Res. 1986 Nov 11;14(21):8625-35 PMID: 3024112
  26. Trimethoprim R factors in enterobacteria from clinical specimens.
    J Med Microbiol. 1974 May;7(2):169-77 PMID: 4599661
  27. Transposition of R factor genes to bacteriophage lambda.
    Proc Natl Acad Sci U S A. 1975 Sep;72(9):3628-32 PMID: 1059152
  28. Tn402: a new transposable element determining trimethoprim resistance that inserts in bacteriophage lambda.
    J Bacteriol. 1977 Mar;129(3):1632-5 PMID: 321437
  29. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  30. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system.
    Gene. 1977;2(2):95-113 PMID: 344137
  31. Determination of plasmid molecular weights from ultraviolet sensitivities.
    Nature. 1978 Mar 30;272(5652):471-2 PMID: 345128
  32. Genetic complementation between two mutant unc alleles (unc A401 and unc D409) affecting the Fl portion of the magnesium ion-stimulated adenosine triphosphatase of Escherichia coli K12.
    Biochem J. 1978 Mar 15;170(3):593-8 PMID: 148275
  33. Simple method for identification of plasmid-coded proteins.
    J Bacteriol. 1979 Jan;137(1):692-3 PMID: 368040
  34. In vitro packaging of lambda and cosmid DNA.
    Methods Enzymol. 1979;68:299-309 PMID: 161604
  35. Genetic organization of the broad-host-range IncP-1 plasmid R751.
    J Bacteriol. 1980 Sep;143(3):1362-73 PMID: 6251029
  36. DNA sequence of a plasmid-encoded dihydrofolate reductase.
    Mol Gen Genet. 1981;181(4):441-7 PMID: 7022127
  37. Plasmid-determined immunity of Escherichia coli K-12 to colicin Ia Is mediated by a plasmid-encoded membrane protein.
    J Bacteriol. 1981 Dec;148(3):817-28 PMID: 6273383
  38. Analysis of plasmids in nosocomial strains of multiple-antibiotic-resistant Staphylococcus aureus.
    Antimicrob Agents Chemother. 1983 Jun;23(6):817-26 PMID: 6311086
  39. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  40. Cloning and expression of Staphylococcus aureus plasmid-mediated quaternary ammonium resistance in Escherichia coli.
    Antimicrob Agents Chemother. 1985 Jan;27(1):79-83 PMID: 3885846
  41. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors.
    Gene. 1985;33(1):103-19 PMID: 2985470
  42. Nucleotide sequence of an Escherichia coli chromosomal hemolysin.
    J Bacteriol. 1985 Jul;163(1):94-105 PMID: 3891743
  43. The nucleotide sequence of the mercuric resistance operons of plasmid R100 and transposon Tn501: further evidence for mer genes which enhance the activity of the mercuric ion detoxification system.
    Mol Gen Genet. 1986 Jan;202(1):143-51 PMID: 3007931
  44. The integrase family of site-specific recombinases: regional similarities and global diversity.
    EMBO J. 1986 Feb;5(2):433-40 PMID: 3011407
  45. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins.
    Annu Rev Biophys Biophys Chem. 1986;15:321-53 PMID: 3521657
  46. Nucleotide sequence analysis of the trimethoprim resistant dihydrofolate reductase encoded by R plasmid R751.
    Nucleic Acids Res. 1986 Jul 25;14(14):5933 PMID: 3526286
  47. A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons.
    Mol Microbiol. 1989 Dec;3(12):1669-83 PMID: 2560119
  48. Genetic elements involved in Tn21 site-specific integration, a novel mechanism for the dissemination of antibiotic resistance genes.
    EMBO J. 1990 Apr;9(4):1275-81 PMID: 2157593
  49. Cloning of the ethidium efflux gene from Escherichia coli.
    FEMS Microbiol Lett. 1990 Mar 1;56(1-2):73-6 PMID: 2185131
  50. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones.
    J Bacteriol. 1990 Dec;172(12):6942-9 PMID: 2174864
  51. Cloning and sequence analysis of truncated T-DNA inserts from Nicotiana tabacum.
    Gene. 1990 Oct 15;94(2):155-63 PMID: 1701747
  52. Metal-tetracycline/H+ antiporter of Escherichia coli encoded by a transposon Tn10. Histidine 257 plays an essential role in H+ translocation.
    J Biol Chem. 1991 Apr 5;266(10):6045-51 PMID: 1848846
  53. Efflux-mediated antiseptic resistance gene qacA from Staphylococcus aureus: common ancestry with tetracycline- and sugar-transport proteins.
    Mol Microbiol. 1990 Dec;4(12):2051-62 PMID: 2089219
  54. Site-specific insertion of genes into integrons: role of the 59-base element and determination of the recombination cross-over point.
    Mol Microbiol. 1991 Aug;5(8):1941-59 PMID: 1662753
  55. Characterization of In0 of Pseudomonas aeruginosa plasmid pVS1, an ancestor of integrons of multiresistance plasmids and transposons of gram-negative bacteria.
    J Bacteriol. 1992 Feb;174(4):1248-57 PMID: 1310501
  56. Site-specific deletion and rearrangement of integron insert genes catalyzed by the integron DNA integrase.
    J Bacteriol. 1992 Mar;174(5):1574-85 PMID: 1311297
  57. Insertions of resistance genes into Tn21-like transposons.
    J Antimicrob Chemother. 1986 Oct;18 Suppl C:85-92 PMID: 3027019
Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.37.4.761
Published
1993-04-00
Pages
761-8
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC187754
Subset
IM
Databases
GENBANK
L05008, L05009, L05010, L05011, L05012, L05013, L05014, L08748, M97169, X68232
External Links
PubMed source DOI: 10.1128/AAC.37.4.761 PMC Full Text View journal details
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