Emr, an Escherichia coli locus for multidrug resistance.
PDF (1.2M)
Journal: 1992/November - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 1409590
Abstract:
An Escherichia coli chromosomal DNA fragment cloned on a multicopy plasmid conferred resistance to carbonylcyanide m-chlorophenylhydrazone, nalidixic acid, and a number of other toxic compounds. The sequence of the cloned emr locus located at minute 57.5 of the chromosome revealed two open reading frames, emrA and emrB. emrB encodes a highly hydrophobic 56.2-kDa peptide, with 14 potential alpha-helices to span the inner membrane. The peptide is homologous to QacA, a multidrug-resistant pump from Staphylococcus aureus, and belongs to a gene family that includes tetracycline-resistant pumps of Gram-positive bacteria and the galactose/H+ symporter of E. coli. emrA encodes a putative 42.7-kDa peptide containing a single hydrophobic domain and a large C-terminal hydrophilic domain. An active pho-fusion to the C domain suggested that EmrA is a membrane protein. Disruption of emrB significantly increased sensitivity of cells to uncouplers. The cellular content of uncoupler increased in the order: overexpressed emrB cells greater than wild type greater than emrB-.
Open in
PUBMED | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(138)
References
(28)
Drugs
(2)
Chemicals
(7)
Genes
(6)
Organisms
(2)
Processes
(11)
Anatomy
(1)
Affiliates
(1)
Similar articles
Articles by the same authors
Discussion board
Proc Natl Acad Sci U S A 89(19): 8938-8942
PMID: 1409590

Emr, an Escherichia coli locus for multidrug resistance.

Abstract

An Escherichia coli chromosomal DNA fragment cloned on a multicopy plasmid conferred resistance to carbonylcyanide m-chlorophenylhydrazone, nalidixic acid, and a number of other toxic compounds. The sequence of the cloned emr locus located at minute 57.5 of the chromosome revealed two open reading frames, emrA and emrB. emrB encodes a highly hydrophobic 56.2-kDa peptide, with 14 potential alpha-helices to span the inner membrane. The peptide is homologous to QacA, a multidrug-resistant pump from Staphylococcus aureus, and belongs to a gene family that includes tetracycline-resistant pumps of Gram-positive bacteria and the galactose/H+ symporter of E. coli. emrA encodes a putative 42.7-kDa peptide containing a single hydrophobic domain and a large C-terminal hydrophilic domain. An active pho-fusion to the C domain suggested that EmrA is a membrane protein. Disruption of emrB significantly increased sensitivity of cells to uncouplers. The cellular content of uncoupler increased in the order: overexpressed emrB cells greater than wild type greater than emrB-.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
icon of scanned page 8938
8938
icon of scanned page 8939
8939
icon of scanned page 8940
8940
icon of scanned page 8941
8941
icon of scanned page 8942
8942

Images in this article

Image
Image
on p.8939
Image
Image
on p.8941
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Gottesman MM, Pastan I. The multidrug transporter, a double-edged sword. J Biol Chem. 1988 Sep 5;263(25):12163–12166. [PubMed] [Google Scholar]
  • Lyon BR, Skurray R. Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev. 1987 Mar;51(1):88–134.[PMC free article] [PubMed] [Google Scholar]
  • Tennent JM, Lyon BR, Midgley M, Jones IG, Purewal AS, Skurray RA. 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. [PubMed] [Google Scholar]
  • Rouch DA, Cram DS, DiBerardino D, Littlejohn TG, Skurray RA. Efflux-mediated antiseptic resistance gene qacA from Staphylococcus aureus: common ancestry with tetracycline- and sugar-transport proteins. Mol Microbiol. 1990 Dec;4(12):2051–2062. [PubMed] [Google Scholar]
  • Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol. 1990 Dec;172(12):6942–6949.[PMC free article] [PubMed] [Google Scholar]
  • Neyfakh AA, Bidnenko VE, Chen LB. 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):4781–4785.[PMC free article] [PubMed] [Google Scholar]
  • Grinius L, Dreguniene G, Goldberg EB, Liao CH, Projan SJ. A staphylococcal multidrug resistance gene product is a member of a new protein family. Plasmid. 1992 Mar;27(2):119–129. [PubMed] [Google Scholar]
  • Purewal AS, Jones IG, Midgley M. Cloning of the ethidium efflux gene from Escherichia coli. FEMS Microbiol Lett. 1990 Mar 1;56(1-2):73–76. [PubMed] [Google Scholar]
  • Rosner JL, Chai TJ, Foulds J. Regulation of ompF porin expression by salicylate in Escherichia coli. J Bacteriol. 1991 Sep;173(18):5631–5638.[PMC free article] [PubMed] [Google Scholar]
  • Cohen SP, McMurry LM, Levy SB. marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli. J Bacteriol. 1988 Dec;170(12):5416–5422.[PMC free article] [PubMed] [Google Scholar]
  • Krulwich TA, Quirk PG, Guffanti AA. Uncoupler-resistant mutants of bacteria. Microbiol Rev. 1990 Mar;54(1):52–65.[PMC free article] [PubMed] [Google Scholar]
  • Kleckner N, Bender J, Gottesman S. Uses of transposons with emphasis on Tn10. Methods Enzymol. 1991;204:139–180. [PubMed] [Google Scholar]
  • Jasin M, Schimmel P. Deletion of an essential gene in Escherichia coli by site-specific recombination with linear DNA fragments. J Bacteriol. 1984 Aug;159(2):783–786.[PMC free article] [PubMed] [Google Scholar]
  • Boyd D, Manoil C, Beckwith J. Determinants of membrane protein topology. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8525–8529.[PMC free article] [PubMed] [Google Scholar]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed] [Google Scholar]
  • del Castillo I, Gómez JM, Moreno F. mprA, an Escherichia coli gene that reduces growth-phase-dependent synthesis of microcins B17 and C7 and blocks osmoinduction of proU when cloned on a high-copy-number plasmid. J Bacteriol. 1990 Jan;172(1):437–445.[PMC free article] [PubMed] [Google Scholar]
  • Glaser P, Sakamoto H, Bellalou J, Ullmann A, Danchin A. Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis. EMBO J. 1988 Dec 1;7(12):3997–4004.[PMC free article] [PubMed] [Google Scholar]
  • Gilson L, Mahanty HK, Kolter R. Genetic analysis of an MDR-like export system: the secretion of colicin V. EMBO J. 1990 Dec;9(12):3875–3884.[PMC free article] [PubMed] [Google Scholar]
  • Felmlee T, Pellett S, Lee EY, Welch RA. Escherichia coli hemolysin is released extracellularly without cleavage of a signal peptide. J Bacteriol. 1985 Jul;163(1):88–93.[PMC free article] [PubMed] [Google Scholar]
  • Neal RJ, Chater KF. Nucleotide sequence analysis reveals similarities between proteins determining methylenomycin A resistance in Streptomyces and tetracycline resistance in eubacteria. Gene. 1987;58(2-3):229–241. [PubMed] [Google Scholar]
  • Khan SA, Novick RP. Complete nucleotide sequence of pT181, a tetracycline-resistance plasmid from Staphylococcus aureus. Plasmid. 1983 Nov;10(3):251–259. [PubMed] [Google Scholar]
  • Hoshino T, Ikeda T, Tomizuka N, Furukawa K. Nucleotide sequence of the tetracycline resistance gene of pTHT15, a thermophilic Bacillus plasmid: comparison with staphylococcal TcR controls. Gene. 1985;37(1-3):131–138. [PubMed] [Google Scholar]
  • Hane MW, Wood TH. Escherichia coli K-12 mutants resistant to nalidixic acid: genetic mapping and dominance studies. J Bacteriol. 1969 Jul;99(1):238–241.[PMC free article] [PubMed] [Google Scholar]
  • Bourguignon GJ, Levitt M, Sternglanz R. Studies on the mechanism of action of nalidixic acid. Antimicrob Agents Chemother. 1973 Oct;4(4):479–486.[PMC free article] [PubMed] [Google Scholar]
  • Yamaguchi A, Ono N, Akasaka T, Noumi T, Sawai T. Metal-tetracycline/H+ antiporter of Escherichia coli encoded by a transposon, Tn10. The role of the conserved dipeptide, Ser65-Asp66, in tetracycline transport. J Biol Chem. 1990 Sep 15;265(26):15525–15530. [PubMed] [Google Scholar]
  • Neyfakh AA. 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):484–485.[PMC free article] [PubMed] [Google Scholar]
  • Bayer MH, Costello GP, Bayer ME. Isolation and partial characterization of membrane vesicles carrying markers of the membrane adhesion sites. J Bacteriol. 1982 Feb;149(2):758–767.[PMC free article] [PubMed] [Google Scholar]
  • Levy SB. Active efflux mechanisms for antimicrobial resistance. Antimicrob Agents Chemother. 1992 Apr;36(4):695–703.[PMC free article] [PubMed] [Google Scholar]
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Copyright notice
Abstract
An Escherichia coli chromosomal DNA fragment cloned on a multicopy plasmid conferred resistance to carbonylcyanide m-chlorophenylhydrazone, nalidixic acid, and a number of other toxic compounds. The sequence of the cloned emr locus located at minute 57.5 of the chromosome revealed two open reading frames, emrA and emrB. emrB encodes a highly hydrophobic 56.2-kDa peptide, with 14 potential alpha-helices to span the inner membrane. The peptide is homologous to QacA, a multidrug-resistant pump from Staphylococcus aureus, and belongs to a gene family that includes tetracycline-resistant pumps of Gram-positive bacteria and the galactose/H+ symporter of E. coli. emrA encodes a putative 42.7-kDa peptide containing a single hydrophobic domain and a large C-terminal hydrophilic domain. An active pho-fusion to the C domain suggested that EmrA is a membrane protein. Disruption of emrB significantly increased sensitivity of cells to uncouplers. The cellular content of uncoupler increased in the order: overexpressed emrB cells greater than wild type greater than emrB-.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.