• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. Apr 1992; 36(4): 695–703.
PMCID: PMC189356

Active efflux mechanisms for antimicrobial resistance.

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 (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ball PR, Shales SW, Chopra I. Plasmid-mediated tetracycline resistance in Escherichia coli involves increased efflux of the antibiotic. Biochem Biophys Res Commun. 1980 Mar 13;93(1):74–81. [PubMed]
  • Beck JC, Rosen BP. Cation/proton antiport systems in escherichia coli: properties of the sodium/proton antiporter. Arch Biochem Biophys. 1979 Apr 15;194(1):208–214. [PubMed]
  • Bissonnette L, Champetier S, Buisson JP, Roy PH. Characterization of the nonenzymatic chloramphenicol resistance (cmlA) gene of the In4 integron of Tn1696: similarity of the product to transmembrane transport proteins. J Bacteriol. 1991 Jul;173(14):4493–4502. [PMC free article] [PubMed]
  • Brey RN, Rosen BP. Cation/proton antiport systems in Escherichia coli. Properties of the calcium/proton antiporter. J Biol Chem. 1979 Mar 25;254(6):1957–1963. [PubMed]
  • Brey RN, Rosen BP, Sorensen EN. Cation/proton antiport systems in Escherichia coli. Properties of the potassium/proton antiporter. J Biol Chem. 1980 Jan 10;255(1):39–44. [PubMed]
  • Celesk RA, Robillard NJ. Factors influencing the accumulation of ciprofloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1989 Nov;33(11):1921–1926. [PMC free article] [PubMed]
  • Cervantes C, Ohtake H, Chu L, Misra TK, Silver S. Cloning, nucleotide sequence, and expression of the chromate resistance determinant of Pseudomonas aeruginosa plasmid pUM505. J Bacteriol. 1990 Jan;172(1):287–291. [PMC free article] [PubMed]
  • Cohen SP, Hooper DC, Wolfson JS, Souza KS, McMurry LM, Levy SB. Endogenous active efflux of norfloxacin in susceptible Escherichia coli. Antimicrob Agents Chemother. 1988 Aug;32(8):1187–1191. [PMC free article] [PubMed]
  • Cohen SP, McMurry LM, Hooper DC, Wolfson JS, Levy SB. Cross-resistance to fluoroquinolones in multiple-antibiotic-resistant (Mar) Escherichia coli selected by tetracycline or chloramphenicol: decreased drug accumulation associated with membrane changes in addition to OmpF reduction. Antimicrob Agents Chemother. 1989 Aug;33(8):1318–1325. [PMC free article] [PubMed]
  • Coleman DC, Chopra I, Shales SW, Howe TG, Foster TJ. Analysis of tetracycline resistance encoded by transposon Tn10: deletion mapping of tetracycline-sensitive point mutations and identification of two structural genes. J Bacteriol. 1983 Feb;153(2):921–929. [PMC free article] [PubMed]
  • Connamacher RH, Mandel HG, Hahn FE. Adaptation of populations of Bacillus cereus to tetracycline. Mol Pharmacol. 1967 Nov;3(6):586–594. [PubMed]
  • Curiale MS, Levy SB. Two complementation groups mediate tetracycline resistance determined by Tn10. J Bacteriol. 1982 Jul;151(1):209–215. [PMC free article] [PubMed]
  • Curiale MS, McMurry LM, Levy SB. Intracistronic complementation of the tetracycline resistance membrane protein of Tn10. J Bacteriol. 1984 Jan;157(1):211–217. [PMC free article] [PubMed]
  • Dano K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta. 1973 Oct 25;323(3):466–483. [PubMed]
  • Deuchars KL, Ling V. P-glycoprotein and multidrug resistance in cancer chemotherapy. Semin Oncol. 1989 Apr;16(2):156–165. [PubMed]
  • Dorman CJ, Foster TJ, Shaw WV. Nucleotide sequence of the R26 chloramphenicol resistance determinant and identification of its gene product. Gene. 1986;41(2-3):349–353. [PubMed]
  • Eckert B, Beck CF. Topology of the transposon Tn10-encoded tetracycline resistance protein within the inner membrane of Escherichia coli. J Biol Chem. 1989 Jul 15;264(20):11663–11670. [PubMed]
  • Fernández-Moreno MA, Caballero JL, Hopwood DA, Malpartida F. The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. Cell. 1991 Aug 23;66(4):769–780. [PubMed]
  • Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature. 1990 May 17;345(6272):255–258. [PubMed]
  • George AM, Levy SB. Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline. J Bacteriol. 1983 Aug;155(2):531–540. [PMC free article] [PubMed]
  • George AM, Levy SB. Gene in the major cotransduction gap of the Escherichia coli K-12 linkage map required for the expression of chromosomal resistance to tetracycline and other antibiotics. J Bacteriol. 1983 Aug;155(2):541–548. [PMC free article] [PubMed]
  • Goldman RC, Capobianco JO. Role of an energy-dependent efflux pump in plasmid pNE24-mediated resistance to 14- and 15-membered macrolides in Staphylococcus epidermidis. Antimicrob Agents Chemother. 1990 Oct;34(10):1973–1980. [PMC free article] [PubMed]
  • 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]
  • Harold FM, Papineau D. Cation transport and electrogenesis by Streptococcus faecalis. II. Proton and sodium extrusion. J Membr Biol. 1972;8(1):45–62. [PubMed]
  • Hickman RK, Levy SB. Evidence that TET protein functions as a multimer in the inner membrane of Escherichia coli. J Bacteriol. 1988 Apr;170(4):1715–1720. [PMC free article] [PubMed]
  • 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]
  • Jorgensen RA, Reznikoff WS. Organization of structural and regulatory genes that mediate tetracycline resistance in transposon Tn10. J Bacteriol. 1979 Jun;138(3):705–714. [PMC free article] [PubMed]
  • Kaatz GW, Seo SM, Ruble CA. Mechanisms of fluoroquinolone resistance in Staphylococcus aureus. J Infect Dis. 1991 May;163(5):1080–1086. [PubMed]
  • Kamimoto Y, Gatmaitan Z, Hsu J, Arias IM. The function of Gp170, the multidrug resistance gene product, in rat liver canalicular membrane vesicles. J Biol Chem. 1989 Jul 15;264(20):11693–11698. [PubMed]
  • Kaneko M, Yamaguchi A, Sawai T. Energetics of tetracycline efflux system encoded by Tn10 in Escherichia coli. FEBS Lett. 1985 Dec 2;193(2):194–198. [PubMed]
  • Kobayashi H, Van Brunt J, Harold FM. ATP-linked calcium transport in cells and membrane vesicles of Streptococcus faecalis. J Biol Chem. 1978 Apr 10;253(7):2085–2092. [PubMed]
  • Krogstad DJ, Gluzman IY, Kyle DE, Oduola AM, Martin SK, Milhous WK, Schlesinger PH. Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance. Science. 1987 Nov 27;238(4831):1283–1285. [PubMed]
  • Kushner DJ, Khan SR. Proflavine Uptake and Release in Sensitive and Resistant Escherichia coli. J Bacteriol. 1968 Oct;96(4):1103–1114. [PMC free article] [PubMed]
  • Lambert B, Le Pecq JB. Effect of mutation, electric membrane potential, and metabolic inhibitors on the accessibility of nucleic acids to ethidium bromide in Escherichia coli cells. Biochemistry. 1984 Jan 3;23(1):166–176. [PubMed]
  • Lampson BC, von David W, Parisi JT. Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis. Antimicrob Agents Chemother. 1986 Nov;30(5):653–658. [PMC free article] [PubMed]
  • Levy SB. Evolution and spread of tetracycline resistance determinants. J Antimicrob Chemother. 1989 Jul;24(1):1–3. [PubMed]
  • Levy SB, McMurry L. Detection of an inducible membrane protein associated with R-factor-mediated tetracycline resistance. Biochem Biophys Res Commun. 1974 Feb 27;56(4):1060–1068. [PubMed]
  • Levy SB, McMurry L. Plasmid-determined tetracycline resistance involves new transport systems for tetracycline. Nature. 1978 Nov 2;276(5683):90–92. [PubMed]
  • Littlejohn TG, DiBerardino D, Messerotti LJ, Spiers SJ, Skurray RA. Structure and evolution of a family of genes encoding antiseptic and disinfectant resistance in Staphylococcus aureus. Gene. 1991 May 15;101(1):59–66. [PubMed]
  • Marquardt D, McCrone S, Center MS. Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. Cancer Res. 1990 Mar 1;50(5):1426–1430. [PubMed]
  • Martin SK, Oduola AM, Milhous WK. Reversal of chloroquine resistance in Plasmodium falciparum by verapamil. Science. 1987 Feb 20;235(4791):899–901. [PubMed]
  • McMurry L, Petrucci RE, Jr, Levy SB. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3974–3977. [PMC free article] [PubMed]
  • McMurry LM, Aronson DA, Levy SB. Susceptible Escherichia coli cells can actively excrete tetracyclines. Antimicrob Agents Chemother. 1983 Oct;24(4):544–551. [PMC free article] [PubMed]
  • McMurry LM, Park BH, Burdett V, Levy SB. Energy-dependent efflux mediated by class L (tetL) tetracycline resistance determinant from streptococci. Antimicrob Agents Chemother. 1987 Oct;31(10):1648–1650. [PMC free article] [PubMed]
  • Midgley M. The phosphonium ion efflux system of Escherichia coli: relationship to the ethidium efflux system and energetic studies. J Gen Microbiol. 1986 Nov;132(11):3187–3193. [PubMed]
  • Mobley HL, Rosen BP. Energetics of plasmid-mediated arsenate resistance in Escherichia coli. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6119–6122. [PMC free article] [PubMed]
  • Mojumdar M, Khan SA. Characterization of the tetracycline resistance gene of plasmid pT181 of Staphylococcus aureus. J Bacteriol. 1988 Dec;170(12):5522–5528. [PMC free article] [PubMed]
  • Nakamura H. Acriflavine-binding capacity of Escherichia coli in relation to acriflavine sensitivity and metabolic activity. J Bacteriol. 1966 Nov;92(5):1447–1452. [PMC free article] [PubMed]
  • Nakamura T, Hsu C, Rosen BP. Cation/proton antiport systems in Escherichia coli. Solubilization and reconstitution of delta pH-driven sodium/proton and calcium/proton antiporters. J Biol Chem. 1986 Jan 15;261(2):678–683. [PubMed]
  • 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]
  • 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]
  • 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]
  • Nies A, Nies DH, Silver S. Nucleotide sequence and expression of a plasmid-encoded chromate resistance determinant from Alcaligenes eutrophus. J Biol Chem. 1990 Apr 5;265(10):5648–5653. [PubMed]
  • Nies DH, Nies A, Chu L, Silver S. Expression and nucleotide sequence of a plasmid-determined divalent cation efflux system from Alcaligenes eutrophus. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7351–7355. [PMC free article] [PubMed]
  • Nies DH, Silver S. Plasmid-determined inducible efflux is responsible for resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus. J Bacteriol. 1989 Feb;171(2):896–900. [PMC free article] [PubMed]
  • Nucifora G, Chu L, Misra TK, Silver S. Cadmium resistance from Staphylococcus aureus plasmid pI258 cadA gene results from a cadmium-efflux ATPase. Proc Natl Acad Sci U S A. 1989 May;86(10):3544–3548. [PMC free article] [PubMed]
  • Ohnuki T, Katoh T, Imanaka T, Aiba S. Molecular cloning of tetracycline resistance genes from Streptomyces rimosus in Streptomyces griseus and characterization of the cloned genes. J Bacteriol. 1985 Mar;161(3):1010–1016. [PMC free article] [PubMed]
  • Ohshita Y, Hiramatsu K, Yokota T. A point mutation in norA gene is responsible for quinolone resistance in Staphylococcus aureus. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1028–1034. [PubMed]
  • Park BH, Levy SB. The cryptic tetracycline resistance determinant on Tn4400 mediates tetracycline degradation as well as tetracycline efflux. Antimicrob Agents Chemother. 1988 Dec;32(12):1797–1800. [PMC free article] [PubMed]
  • 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]
  • Reynes JP, Calmels T, Drocourt D, Tiraby G. Cloning, expression in Escherichia coli and nucleotide sequence of a tetracycline-resistance gene from Streptomyces rimosus. J Gen Microbiol. 1988 Mar;134(3):585–598. [PubMed]
  • Rosen BP, Borbolla MG. A plasmid-encoded arsenite pump produces arsenite resistance in Escherichia coli. Biochem Biophys Res Commun. 1984 Nov 14;124(3):760–765. [PubMed]
  • Rosen BP, McClees JS. Active transport of calcium in inverted membrane vesicles of Escherichia coli. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5042–5046. [PMC free article] [PubMed]
  • Ross JI, Eady EA, Cove JH, Cunliffe WJ, Baumberg S, Wootton JC. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol. 1990 Jul;4(7):1207–1214. [PubMed]
  • 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]
  • Rubin RA, Levy SB. Interdomain hybrid Tet proteins confer tetracycline resistance only when they are derived from closely related members of the tet gene family. J Bacteriol. 1990 May;172(5):2303–2312. [PMC free article] [PubMed]
  • Rubin RA, Levy SB. Tet protein domains interact productively to mediate tetracycline resistance when present on separate polypeptides. J Bacteriol. 1991 Jul;173(14):4503–4509. [PMC free article] [PubMed]
  • Rubin RA, Levy SB, Heinrikson RL, Kézdy FJ. Gene duplication in the evolution of the two complementing domains of gram-negative bacterial tetracycline efflux proteins. Gene. 1990 Mar 1;87(1):7–13. [PubMed]
  • Safa AR, Glover CJ, Meyers MB, Biedler JL, Felsted RL. Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J Biol Chem. 1986 May 15;261(14):6137–6140. [PubMed]
  • Sasatsu M, Shima K, Shibata Y, Kono M. 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):10103–10103. [PMC free article] [PubMed]
  • Siddiqui RA, Benthin K, Schlegel HG. Cloning of pMOL28-encoded nickel resistance genes and expression of the genes in Alcaligenes eutrophus and Pseudomonas spp. J Bacteriol. 1989 Sep;171(9):5071–5078. [PMC free article] [PubMed]
  • Silver S, Keach D. Energy-dependent arsenate efflux: the mechanism of plasmid-mediated resistance. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6114–6118. [PMC free article] [PubMed]
  • Silver S, Nucifora G, Chu L, Misra TK. Bacterial resistance ATPases: primary pumps for exporting toxic cations and anions. Trends Biochem Sci. 1989 Feb;14(2):76–80. [PubMed]
  • Silver S, Walderhaug M. Gene regulation of plasmid- and chromosome-determined inorganic ion transport in bacteria. Microbiol Rev. 1992 Mar;56(1):195–228. [PMC free article] [PubMed]
  • Skovsgaard T. Mechanisms of resistance to daunorubicin in Ehrlich ascites tumor cells. Cancer Res. 1978 Jun;38(6):1785–1791. [PubMed]
  • Slapak CA, Daniel JC, Levy SB. Sequential emergence of distinct resistance phenotypes in murine erythroleukemia cells under adriamycin selection: decreased anthracycline uptake precedes increased P-glycoprotein expression. Cancer Res. 1990 Dec 15;50(24):7895–7901. [PubMed]
  • 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]
  • Tisa LS, Rosen BP. Transport systems encoded by bacterial plasmids. J Bioenerg Biomembr. 1990 Aug;22(4):493–507. [PubMed]
  • Tsai KJ, Yoon KP, Lynn AR. ATP-dependent cadmium transport by the cadA cadmium resistance determinant in everted membrane vesicles of Bacillus subtilis. J Bacteriol. 1992 Jan;174(1):116–121. [PMC free article] [PubMed]
  • Tynecka Z, Gos Z, Zajac J. Energy-dependent efflux of cadmium coded by a plasmid resistance determinant in Staphylococcus aureus. J Bacteriol. 1981 Aug;147(2):313–319. [PMC free article] [PubMed]
  • Walter EG, Weiner JH, Taylor DE. Nucleotide sequence and overexpression of the tellurite-resistance determinant from the IncHII plasmid pHH1508a. Gene. 1991 May 15;101(1):1–7. [PubMed]
  • West IC, Mitchell P. Proton/sodium ion antiport in Escherichia coli. Biochem J. 1974 Oct;144(1):87–90. [PMC free article] [PubMed]
  • Wilson CM, Serrano AE, Wasley A, Bogenschutz MP, Shankar AH, Wirth DF. Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum. Science. 1989 Jun 9;244(4909):1184–1186. [PubMed]
  • Yamaguchi A, Udagawa T, Sawai T. Transport of divalent cations with tetracycline as mediated by the transposon Tn10-encoded tetracycline resistance protein. J Biol Chem. 1990 Mar 25;265(9):4809–4813. [PubMed]
  • Yoon KP, Silver S. A second gene in the Staphylococcus aureus cadA cadmium resistance determinant of plasmid pI258. J Bacteriol. 1991 Dec;173(23):7636–7642. [PMC free article] [PubMed]
  • 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]
  • Yoshida S, Kojima T, Inoue M, Mitsuhashi S. Uptake of sparfloxacin and norfloxacin by clinical isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Feb;35(2):368–370. [PMC free article] [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...