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Resolving the Antibiotic Paradox pp 27–69Cite as

Aminoglycoside Antibiotics

Structures, Functions, and Resistance

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 456))

Abstract

The aminoglycoside-aminocyclitol antibiotics (hereafter termed aminoglycosides) are a large family of water soluble, cationic molecules which exhibit broad antimicrobial spectra. While the moniker aminoglycoside refers to a vast array of structurally diverse compounds, they all share the incorporation of a six-membered aminocyclitol ring (Fig. 1). The aminoglycosides find use in the treatment of many bacterial infections caused by both Gram-positive and Gram-negative organisms, and are generally administered by injection or intravenously as a result of their relatively poor oral absorption (Edson and Terrell, 1991). Despite some problems of toxicity and bacterial resistance (described in detail below), these antibiotics continue to be a critically important component of our modern antimicrobial arsenal.

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References

  • Ainsa, J.A., Pérez, E., Pelicic, V., Berthet, F.X., Gicquel, B. and Martin, C., 1997, Aminoglycoside 2′-N-acetyl-transferase genes are universally present in mycobacteria: characterization of the aac(2 ′)-Ic gene from Mycobacterium tuberculosis and the aac(2′)-Id gene from Mycobacterium smegmatis, Mol. Microbiol 24:431–441.

    PubMed  CAS  Google Scholar 

  • Ali, B.H., 1995, Gentamicin nephrotoxicity in humans and animals: some recent research, Gen. Pharmacol 26:1477–1487.

    PubMed  CAS  Google Scholar 

  • Allen, N.E., Jr., W.E.A., Jr., J.N.H. and Kirst, H.A., 1982, 7-Hydroxytropolone: An inhibitor of aminoglycoside-2”-O-adenyltransferase, Antimicrob. Agents Chemother 22:824–831.

    PubMed  CAS  Google Scholar 

  • Azucena, E., Grapsas, I. and Mobashery, S., 1997, Properties of a bifunctional bacterial antibiotic resistance enzyme that catalyzes ATP-dependent 2”-phosphorylation and acetyl-CoA-dependent 6’-acetylation of aminoglycosides, J. Am. Chem. Soc 119:2317–2318.

    CAS  Google Scholar 

  • Bakker, E.P., 1992, Aminoglycoside and aminocyclitol antibiotics: hygromycin B is an atypical bactericidal compound that exerts effects on cells of Escherichia coli characteristic for bacteriostatic aminocyclitols, J. Gen. Microbiol 138:563–569.

    PubMed  CAS  Google Scholar 

  • Beauclerk, A.A. and Cundliffe, E., 1987, Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides, J. Mol. Biol 93:661–671.

    Google Scholar 

  • Beck, E., Ludwig, G., Auerswald, E.A., Reiss, B. and Schaller, H., 1982, Nucleotide sequence and exact localization of the neomycin phosphotransferase gene from transposon Tn5, Gene 19:327–336.

    PubMed  CAS  Google Scholar 

  • Benveniste, R. and Davies, J., 1973, Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria, Proc. Natl. Acad. Sci. USA 70:2276–2280.

    PubMed  CAS  Google Scholar 

  • Berman, J.D. and Fleckenstein, L., 1991, Pharmacokinetic justification of antiprotozoal therapy. AUS perspective, Clin. Pharmacokinet 21:479–493.

    PubMed  CAS  Google Scholar 

  • Blázquez, J., Davies, J. and Moreno, F., 1991, Mutations in the aphA-2 gene of transposon Tn5 mapping within the regions highly conserved in aminoglycoside-phosphotransferases strongly reduce aminoglycoside resistance, Mol Microbiol 5:1511–1518.

    PubMed  Google Scholar 

  • Bochner, B.R. and Ames, B.N., 1982, Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography, J. Biol. Chem 257:9759–9769.

    PubMed  CAS  Google Scholar 

  • Bongaerts, G.P.A. and Molendijk, L., 1984, Relation between aminoglycoside 2”-O-nucleotidyltransferase activity and aminoglycoside resistance, Antimicrob. Agents Chemother 25:234–237.

    PubMed  CAS  Google Scholar 

  • Bräu, B. and Piepersburg, W., 1985, Purification and characterization of a plasmid-encoded aminoglycoside-(3)-N-acetyltransferase IV from Escherichia coli, FEBS Letts 185:43–46.

    Google Scholar 

  • Bräu, B., Pilz, U. and Piepersberg, W., 1984, Genes for gentamicin-(3)-N-acetyltransferases III and IV: I. Nucleotide sequence of the AAC(3)-IV gene and possible involvement of an IS140 element in its expression, Mol. Gen. Genet 193:179–187.

    PubMed  Google Scholar 

  • Brenner, S., 1987, Phosphotransferase sequence homology, Nature. 329:21.

    PubMed  CAS  Google Scholar 

  • Bryan, L.E. (1984), Aminoglycoside resistance, in Antimicrobial Drug Resistance (L. E. Bryan, Ed.) pp 241–277, Academic Press, Orlando.

    Google Scholar 

  • Bryan, L.E. and Kwan, S., 1983, Roles of ribosomal binding, membrane potential, and electron transport in bacterial uptake of streptomycin and gentamicin., Antimicrob. Agents Chemother. 23:835–845.

    PubMed  CAS  Google Scholar 

  • Bryan, L.E. and Van Den Elzen, H.M., 1977, Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria, Antimicrob. Agents Chemother. 12:163–177.

    PubMed  CAS  Google Scholar 

  • Busse, H.-J., Wöstmann, C. and Bakker, E.P., 1992, The bactericidal action of streptomycin: membrane permeabi-lization caused by the insertion of mistranslated proteins into the cytoplasmic membrane of Escherichia coli and subsequent caging of the antibiotic inside the cells due to degradation of these proteins, J. Gen. Microbiol 138:551–561.

    PubMed  CAS  Google Scholar 

  • Chow, J.W., Zervos, M.J., Lerner, S.A., Thal, L.A., Donabedian, S.M., Jaworski, D.D., Tsai, S., Shaw, K.J. and Clewell, D.B., 1997, A novel gentamicin resistance gene in Enterococcus, Antimicrob. Agents Chemother. 41:511–514.

    PubMed  CAS  Google Scholar 

  • Clarke, A.J., 1993, Extent of peptidoglycan O acetylation in the tribe Proteeae, J. Bacteriol 175:4550–4553.

    PubMed  CAS  Google Scholar 

  • Clarke, A. J., Francis, D. and Keenleyside, W.J., 1996, The prevalence of gentamicin 2’-N-acetyltransferase in the Proteeae and its role in the O-acetylation of peptidoglycan, FEMS Microbiol. Lett 145:201–207.

    PubMed  CAS  Google Scholar 

  • Cole, P.A., Grace, M.R., Phillips, R.S., Burn, P. and Walsh, C.T., 1995, The role of the catalytic base in the protein tyrosine kinase Csk, J. Biol. Chem 270:22105–22108.

    PubMed  CAS  Google Scholar 

  • Cortopassi, G. and Hutchin, T., 1994, A molecular and cellular hypothesis for aminoglycoside-induced deafness, Hear. Res 78:27–30.

    PubMed  CAS  Google Scholar 

  • Costa, Y., Galimand, M., Leclercq, R., Duval, J. and Courvalin, P., 1993, Characterization of the chromosomal aac(6′)-li gene specific for Enterococcus faecium, Aniimicrob. Agents Chemother. 37:1896–1903.

    CAS  Google Scholar 

  • Cox, J.R., McKay, G.A., Wright, G.D. and Serpesu, E.H., 1996, Arrangement of substrates at the active site of an aminoglycoside antibiotic 3′-phosphotransferase as determined by NMR, J. Am. Chem. Soc 118:1295–1301.

    CAS  Google Scholar 

  • Cox, J.R. and Serpersu, E.H., 1997, Biologically important conformations of aminoglycoside antibiotics bound to an aminoglycoside 3′-phosphotransferase as determined by transferred nuclear Overhauser effect spectroscopy, Biochemistry. 36:2353–2359.

    PubMed  CAS  Google Scholar 

  • Crann, S.A., Huang, M.Y., McLaren, J.D. and Schacht, J., 1992, Formation of a toxic metabolite from gentamicin by a hepatic cytosolic fraction, Biochem. Pharmacol 43:1835–1839.

    PubMed  CAS  Google Scholar 

  • Cundliffe, E., 1987, On the nature of antibiotic binding sites in ribosomes, Biochimie. 69:863–869.

    PubMed  CAS  Google Scholar 

  • Daigle, D.M., McKay, G.A. and Wright, G.D., 1997, Inhibition of aminoglycoside antibiotic resistance enzymes by protein kinase inhibitors, J. Biol. Chem 272: 24755–24758.

    PubMed  CAS  Google Scholar 

  • Davis, B.D., 1987, Mechanism of action of aminoglycosides, Microbiol. Rev 51:341–350.

    PubMed  CAS  Google Scholar 

  • Davis, B.D., Chen, L.L. and Tai, P.C., 1986, Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides, Proc. Natl. Acad. Sci. USA 83:6164–6168.

    PubMed  CAS  Google Scholar 

  • DeHertogh, D.A. and Lerner, S.A., 1985, Correlation of aminoglycoside resistance with K m s and V max/K m ratios of enzymatic modification of aminoglycosides by 2″-O-nucleotidyltransferase, Antimicrob. Agents Chemother. 27:670–671.

    PubMed  CAS  Google Scholar 

  • DiGiammarino, E.L., Draker, K.a., Wright, G.D. and Serpesu, E.H., 1997, Solution studies of isepamicin and conformational comparisons between isepamicin and butirosin A when bound to an aminoglycoside 6-N-ace-tyltransferase determined by NMR spectroscopy, Biochemistry, in press.

    Google Scholar 

  • Distler, J., Braun, C., Ebert, A. and Piepersberg, W., 1987, Gene cluster for streptomycin biosynthesis in Strep-tomyces griseus: analysis of a central region including the major resistance gene, Mol. Gen. Genet 208:204–210.

    PubMed  CAS  Google Scholar 

  • Dubin, D.T. and Davis, B.D., 1961, The effect of streptomycin on potassium flux in Escherichia coli, Biochim. Biophys. Acta 52:400–402.

    PubMed  CAS  Google Scholar 

  • Edson, R.S. and Terrell, C.L., 1991, The aminoglycosides, Mayo. Clin. Proc 66:1158–1164.

    PubMed  CAS  Google Scholar 

  • Ferretti, J.J., Gilmore, K.S. and Courvalin, P., 1986, Nucleotide sequence analysis of the gene specifying the bi-functional 6′-aminoglycoside acetyltransferase 2″-aminoglycoside phosphotransferase enzyme in Streptococcus faecalis and identification and cloning of gene regions specifying the two activities, J. Bacteriol 167:631–638.

    PubMed  CAS  Google Scholar 

  • Fichtenbaum, C.J., Ritechie, D.J. and Powderly, W.G., 1994, Use of paromomycin for treatment of crypto-sporidiosis in patients with AIDS, Clin. Infect. Dis 16:298–300.

    Google Scholar 

  • Findly, R.C., Gillies, R.J. and Shulman, R.G., 1983, In vivo phosphorus-31 nuclear magnetic resonance reveals lowered ATP during heat shock of Tetrahymena, Science 219:1223–1225.

    PubMed  CAS  Google Scholar 

  • Fourmy, D., Recht, M.I., Blanchard, S.C. and Puglisi, J.D., 1996, Structure of the A site of Escherichia coli 16S ri-bosomal RNA complexed with an aminoglycoside antibiotic, Science. 274:1367–1371.

    PubMed  CAS  Google Scholar 

  • Gates, C.A. and Northrop, D.B., 1988a, Alternative substrate and inhibition kinetics of aminoglycoside nucleotidyltransferase 2″-I in support of a Theorell-Chance kinetic mechanism, Biochemistry. 27:3826–3833.

    PubMed  CAS  Google Scholar 

  • Gates, C.A. and Northrop, D.B., 1988b, Determination of the rate-limiting segment of aminoglycoside nucleotidyltransferase 2″-I by pH-and viscosity-dependent kinetics, Biochemistry. 27:3834–3842.

    PubMed  CAS  Google Scholar 

  • Gates, C.A. and Northrop, D.B., 1988c, Substrate specificities and structure-activity relationships for the nu-cleotidylation of antibiotics catalyzed by aminoglycoside nucleotidytransferase 2″-I, Biochemistry. 27:3820–3825.

    PubMed  CAS  Google Scholar 

  • Gilman, S. and Saunders, V.A., 1986, Accumulation of gentamicin by Staphylococcus aureus: the role of the transmembrane electrical potential, J. Antimicrob. Chemother. (17):31–44.

    Google Scholar 

  • Gorini, L. (1974), Streptomycin and misreading of the genetic code, in Ribosomes (M. Nomura, A. Tissères and P. Lengyel, Eds.) pp 791–803, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  • Gray, G.S. and Fitch, W.M., 1983, Evolution of antibiotic resistance genes: The DNA sequence of a kanamycin resistance gene from Staphylococcus aureus, Mol. Biol. Evol 1:57–66.

    PubMed  CAS  Google Scholar 

  • Gritz, L. and Davies, J., 1983, Plasmid-encoded hygromycin B resistance: the sequence of hygromycin B phosphotransferase gene and its expression in Escherichia coli and Saccharomyces cerevisiae, Gene 25:179–188.

    PubMed  CAS  Google Scholar 

  • Hancock, R., 1961, Early effects of streptomycin on Bacillus megaterium, J. Bacteriol 88:633–639.

    Google Scholar 

  • Hancock, R.E., 1981, Aminoglycoside uptake and mode of action-with special reference to streptomycin and gentamicin. I. Antagonists and mutants, J. Antimicrob. Chemother. 8:249–276.

    PubMed  CAS  Google Scholar 

  • Hannecart-Pokorni, E., Depuydt, F., de Wit, L., van Bossuyt, E., Content, J. and Vanhoof, R., 1997, Characterization of the 6′-N-aminoglycoside acetyltransferase gene aac(6′)-Il associated with a swll-type inte-gron, Antimicrob. Agents Chemother 41:314–318.

    PubMed  CAS  Google Scholar 

  • Heinzel, P., Werbitzky, O., Distler, J. and Piepersberg, W., 1988, A second streptomycin resistance gene from Streptomyces griseus codes for streptomycin-3″-phosphotransferase. Relationships between antibiotic and protein kinases, Arch. Microbiol 150:184–192.

    PubMed  CAS  Google Scholar 

  • Herbert, C.J., Sarwar, M., Ner, S.S., I.G., G. and Akhtar, M., 1986, Sequence and interspecies transfer of an aminoglycoside phosphotransferase gene (APH) of Bacillus circulans. Self-defence mechanism in antibiotic-producing organisms, Biochem. J 233:383–393.

    Google Scholar 

  • Higgins, C.E. and Kastners, R.E., 1967, Nebramycin, a new broad-spectrum antibiotic complex. II. Description of Streptomyces tenebrarius, Antimicrob. Agetns Chemother. 7:324–331.

    CAS  Google Scholar 

  • Hinshaw, H.C. and Feldman, W.H., 1945, Streptomycin in treatment of clinical tuberculosis: preliminary report, Mayo Clin 20:313–318.

    Google Scholar 

  • Hodel-Christian, S.L. and Murray, B.E., 1991, Characterization of the gentamicin resistance transposon Tn5281 from Enterococcus faecalis and comparison to staphylococcal transposons Tn4001 and Tn403I, Antimicrob. Agents Chemother. 35:1147–1152.

    PubMed  CAS  Google Scholar 

  • Hollingshead, S. and Vapnek, D., 1985, Nucleotide sequence analysis of a gene encoding a streptomycin/specti-nomycin adenyltransferase, Plasmid 13:17–30.

    PubMed  CAS  Google Scholar 

  • Holm, L. and Sander, C., 1995, DNA polymerase β belongs to an ancient nucleotidyltransferase superfamily, Trends Biol. Chem 20:345–347.

    CAS  Google Scholar 

  • Holmes, D.J. and Cundliffe, E., 1991, Analysis of a ribosomal RNA methylase gene from Streptomyces tene-brarius which confers resistance to gentamicin, Mol. Gen. Genet 229:229–237.

    PubMed  CAS  Google Scholar 

  • Holmes, D.J., Drocourt, D., Tiraby, G. and Cundliffe, E., 1991, Cloning of an aminoglycoside-resistance-encoding gene, kamC, from Saccharopolyspora hirsuta: comparison with kamB from Streptomyces tenebrarius, Gene 102:19–26.

    PubMed  CAS  Google Scholar 

  • Hon, W.C., McKay, G.A., Thompson, P.R., Sweet, R.M., Yang, D.S.C., Wright, G.D. and Berghuis, A.M., 1997, Structure of an enzyme required for aminoglycoside resistance reveals homology to eukariotic protein kinases, Cell 89:887–895.

    PubMed  CAS  Google Scholar 

  • Hoshiko, S., Nojiri, C., Matsunaga, K., Katsumata, K., Satoh, E. and Nagaoka, K., 1988, Nucleotide sequence of the ribostamycin phosphotransferase gene and of its control region in Streptomyces ribosidificus, Gene 68:285–296.

    PubMed  CAS  Google Scholar 

  • Hotta, K., Zhu, C.B., Ogata, T., Sunada, A., Ishikawa, J., Mizuno, S., Ikeda, Y. and Kondo, S., 1996, Enzymatic 2′-N-acetylation of arbekacin and antibiotic activity of its product, J. Antibiot 49:458–464.

    PubMed  CAS  Google Scholar 

  • Hubbard, S.R., Wei, L., Ellis, L. and Hendrickson, W.A., 1994, Crystal structure of the tyrosine kinase domain of the human insulin receptor, Nature 372:746–754.

    PubMed  CAS  Google Scholar 

  • Humbert, R. and Altendorf, K., 1989, Defective gamma subunit of ATP synthase (F1F0) from Escherichia coli leads to resistance to aminoglycoside antibiotics, J. Bacteriol 171:1435–1444.

    PubMed  CAS  Google Scholar 

  • Hutchin, T. and Cortopassi, G., 1994, Proposed molecular and cellular mechanism for aminoglycoside ototoxicity, Antimicrob. Agents Chemother. 38:2517–2520.

    PubMed  CAS  Google Scholar 

  • Ishikawa, J. and Hotta, K., 1991, Nucleotide sequence and transcriptional start point of the kan gene encoding an aminoglycoside 3-N-acetyltransferase from Streptomyces griseus SS-1198PR, Gene 108:127–132.

    PubMed  CAS  Google Scholar 

  • Johnson, L.N., Noble, M.E. and Owen, D.J., 1996, Active and inactive protein kinases: structural basis for regulation, Cell 85:149–158.

    PubMed  CAS  Google Scholar 

  • Jones, R.L.D., Jaskula, J.C. and Janssen, G.R., 1992, In vivo translational start site selection on leaderless mRNA transcribed from the Streptomyces fradiae aph gene, J. Bacteriol 174:4753–4760.

    PubMed  CAS  Google Scholar 

  • Kabins, S.A., Nathan, C. and Cohen, S., 1976, In vitro comparison of netilmicin, a semisynthetic derivative of sisomicin, and four other aminoglycoside antibiotics, Antimicrob. Agents Chemother. 10:139–145.

    PubMed  CAS  Google Scholar 

  • Kadurugamuwa, J.L., Clarke, A.J. and Beveridge, T.J., 1993, Surface action of gentamicin on Pseudomonas aeruginosa, J. Bacteriol 174:5798–5805.

    Google Scholar 

  • Kaufhold, A., Podbielski, A., Horaud, T. and Ferrieri, P., 1992, Identical genes confer high-level resistance to gentamicin upon Enterococcus faecalis, Enterococccus faecium, and Streptococcus agalactiae, Antimicrob. Agents Chemother 36:1215–1218.

    PubMed  CAS  Google Scholar 

  • Kawaguchi, H., Naito, T., Nakagowa, S. and Fuijawa, K., 1972, BBK8, a new semisynthetic aminoglycoside antibiotic, J. Antibiot 25:695.

    PubMed  CAS  Google Scholar 

  • Kelemen, G.H., Cundliffe, E. and Financsek, I., 1991, Cloning and characterization of gentamicin-resistance genes from Micromonospora purpurea and Micromonospora rosea, Gene 98:53–60.

    PubMed  CAS  Google Scholar 

  • Kennelly, P.J. and Potts, M., 1996, Fancy meeting you here! a fresh look at “prokaryotic” protein phosphorylation, J. Bacteriol 178:4759–4764.

    PubMed  CAS  Google Scholar 

  • Kettner, M., Macickova, T. and Kremery, V.J. (1991), in Antimicrobial Chemotherapy in Immunocompromised Host, International Congress of Chemotherapy pp 273–275, Berlin.

    Google Scholar 

  • Knighton, D.R., Zheng, J.H., Ten Eyck, L.F., Ashford, V.A., Xuong, N.H., Taylor, S.S. and Sowadski, J.M., 1991, Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase, Science 253:401–14.

    Google Scholar 

  • Kocabiyik, S. and Perlin, M.H., 1992a, Altered substrate specificity by substitutions at Tyr218 in bacterial aminoglycoside 3′-phosphotransferase, FEMS Microbiol. Lett 93:199–202.

    CAS  Google Scholar 

  • Kocabiyik, S. and Perlin, M.H., 1992b, Site-specific mutations of conserved C-terminal residues in aminoglycoside 3′-phosphotransferase II: Phenotypic and structural analysis of mutant enzymes, Biochem. Biophys. Res. Commun 185:925–931.

    PubMed  CAS  Google Scholar 

  • Kocabiyik, S. and Perlin, M.H., 1994, Amino acid substitutions within the analogous nucleotide binding loop (P-loop) of aminoglycoside 3′-phosphotransferase-II, Int. J. Biochem 26:61–66.

    Google Scholar 

  • Kojic, M., Topisirovic, L. and Vasiljevic, B., 1992, Cloning and characterization of an aminoglycoside resistance determinant from Micromonospora zionensis, J. Bacteriol 174:7868–7872.

    PubMed  CAS  Google Scholar 

  • Kondo, S., Tamura, A., Gomi, S., Ikeda, Y., Takeuchi, T. and Mitsuhashi, S., 1993, Structures of enzymatically modified products of arbekacin by methicillin-resistant Staphylococcus aureus, J. Antibiot 46:310–315.

    PubMed  CAS  Google Scholar 

  • Kono, M., Ohmiya, K., Kanda, T., Noguchi, N. and O’hara, K., 1987, Purification and characterization of chromosomal streptomycin adenyltransferase from derivatives of Bacillus subtilis Marburg 168, FEMS Microbiol. Letts 40:223–228.

    CAS  Google Scholar 

  • Lambert, T., Gerbaud, G. and Courvalin, P., 1994a, Characterization of the chromosomal aac(6′)-Ij gene of Acine-tobacter sp. 13 and the aac(6′)-Ih plasmid gene of Acinetobacter baumannii, Antimicrob. Agents Chemother 38:1883–1889.

    PubMed  CAS  Google Scholar 

  • Lambert, T., Ploy, M.-C. and Courvalin, P., 1994b, A spontaneous point mutation in the aac(6′)-Ib′ gene results in altered substrate specificity of aminoglycoside 6′-N-acetyltransferase of a Pseudomonas fluorescens strain, FEMS Microbiol. Lett 115:297–304.

    PubMed  CAS  Google Scholar 

  • Lando, D., Cousin, M.A. and Privat de Garilhe, M., 1973, Misreading, a fundamental aspect of the mechanism of action of several aminoglycosides, Biochemistiy. 12:4528–4533.

    CAS  Google Scholar 

  • Le Goffic, F., Capmau, M.L., Tangy, F. and Baillarge, M., 1979, Mechanism of action of aminoglycoside antibiotics. Binding studies of tobramycin and its 6′-N-acetyl derivative to the bacterial ribosome and its subunits, Eur. J. Biochem 102:73–81.

    PubMed  Google Scholar 

  • LeBlanc, D.J., Lee, L.N. and Inamine, J.M., 1991, Cloning and nucleotide base sequence analysis of a specti-nomycin adenyltransferase AAD(9) determinant from Enterococccus faecalis, Antimicrob. Agents Chemother 35:1804–1810.

    PubMed  CAS  Google Scholar 

  • Leclercq, R. and Courvalin, P., 1991, Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification, Antimicrob. Agents Chemother 35:1267–1272.

    PubMed  CAS  Google Scholar 

  • Lee, K.-Y., Hopkins, J.D. and Syvanen, M., 1991, Evolved neomycin phosphotransferase from an isolate of Klebsiella pneumonia, Mol. Microbiol 5:2039–2046.

    PubMed  CAS  Google Scholar 

  • Lee, S.C., Cleary, P.P. and Gerding, D.N., 1987, More than one DNA sequence encodes the 2″-O-adenylyltrans-ferase phenotype, Antimicrob. Agents Chemother 31:667–670.

    PubMed  CAS  Google Scholar 

  • Lopez-Cabrera, M., Perez-Gonzalez, J.A., Heinzel, P., Piepersberg, W. and Jimenez, A., 1989, Isolation and nucleotide sequencing of an aminocyclitol acetyl transferase gene from Streptomyces rimosus forma paro-momycinus, J. Bacteriol 171:321–328.

    PubMed  CAS  Google Scholar 

  • Lovering, A.M., White, L.O. and Reeves, D.S., 1987, AAC(1): a new aminoglycoside-acetylating enzyme modifying the Cl amino group of apramycin, J. Antimicrob. Chemother 20:803–813.

    PubMed  CAS  Google Scholar 

  • Luzzatto, L., Apirion, D. and Schlessinger, D., 1969, Polyribosome depletion and blockage of the ribosome cycle by streptomycin in Escherichia coli, J. Mol. Biol 42:315–335.

    PubMed  CAS  Google Scholar 

  • Lyutzkanova, D., Distler, J. and Altenbuchner, J., 1997, A spectinomycin resistance determinant from the spe.cti-nomycin producer Streptomyces flavopersicus, Microbiology. 143:2135–2143.

    PubMed  CAS  Google Scholar 

  • Macinga, D.R., Parojcic, M.M. and Rather, P.N., 1995, Identification and analysis of aarP, a transcriptional activator of the 2′-N-acetyltransferase in Providencia stuartii, J. Bacteriol 177:3407–3413.

    PubMed  CAS  Google Scholar 

  • Macinga, D.R. and Rather, P.N., 1996, aarD, a Providencia stuartii homologue of cydD: role in 2′-N-acetyltrans-ferase expression, cell morphology and growth in the presence of an extracellular factor, Mol. Microbiol 19:511–520.

    PubMed  CAS  Google Scholar 

  • Madhusudan, Trafny, E.A., Xuong, N.-H., Adams, J.A., Ten Eyck, L.F., Taylor, S.S. and Sowadski, J.M., 1994, cAMP-dependent protein kinase: Crystallographic insights into substrate recognition and phosphotransfer, Prot. Sci 3:176–187.

    CAS  Google Scholar 

  • Martel, A., Masson, M., Moreau, N. and Goffic, F.L., 1983, Kinetic studies of aminoglycoside acetyl transferase and phosphotransferase from Staphylococcus aureus RPAL, Eur. J. Biochem 133:515–521.

    PubMed  CAS  Google Scholar 

  • Martin, P., Jullien, E. and Courvalin, P., 1988, Nucleotide sequence of Acinetohacter baumannii aphA-6 gene: evolutionary and functional implications of sequence homologies with nucleotide-binding proteins, kinases and other aminoglycoside-modifying enzymes, Mol. Microbiol 2:615–625.

    PubMed  CAS  Google Scholar 

  • Mason, D.J., Dietz, A. and Smith, R.M., 1961, Actinospectacin a new antibiotic.I. Discovery and biological properties, Antibiot. Chemother 11:118–122.

    PubMed  CAS  Google Scholar 

  • Matkovic, B., Piendl, W. and Bock, A., 1984, Ribosomal resistance as a widespread self-defence in aminogly-coside-producing Micromonospora species, FEMS Microbiol. Letts 24:273–276.

    CAS  Google Scholar 

  • Matsumura, M., Katakura, Y., Imanaka, T. and Aiba, S., 1984, Enzymatic and nucleotide sequence studies of a kanamycin-inactivating enzyme encoded by a plasmid from thermophilic bacilli in comparison with that encoded by plasmid pUB110, J. Bacteriol 160:413–420.

    PubMed  CAS  Google Scholar 

  • Matsunaga, K., Yamaki, H., Nishimura, T. and Tanaka, N., 1986, Inhibition of DNA replication initiation by aminoglycoside antibiotics, Antimicrob. Agents Chemother 30:468–474.

    PubMed  CAS  Google Scholar 

  • Mazodier, P., Cossart, P., Giraud, E. and Gasser, F., 1985, Completion of the nucleotide sequence of the central region of Tn5 confirms the presence of three resistance genes, Nucleic Acids Res 13:195–205.

    PubMed  CAS  Google Scholar 

  • McKay, G.A. and Wright, G.D., 1996, Catalytic mechanism of enterococcal kanamycin kinase (APH(3′)-IIIa): Viscosity, thio, and solvent isotope effects support a Theorell-Chance mechanism, Biochemistry. 35:8680–8685.

    PubMed  CAS  Google Scholar 

  • McKay, G.A., Robinson, R.A., Lane, W.S. and Wright, G.D., 1994a, Active-site labeling of an aminoglycoside antibiotic phosphotransferase (APH(3′)-IIIa), Biochemistiy. 33:14115–14120.

    CAS  Google Scholar 

  • McKay, G.A., Roestamadji, J., Mobashery, S. and Wright, G.D., 1996, Recognition of aminoglycoside antibiotics by enterococcal-staphylococcal aminoglycoside 3′-phosphotransferase type IIIa: Role of substrate amino groups, Antimicrob. Agents Chemother 40:2648–2650.

    PubMed  CAS  Google Scholar 

  • McKay, G.A., Thompson, P.R. and Wright, G.D., 1994b, Broad spectrum aminoglycoside phosphotransferase type III from Enterococcus: Overexpression, purification, and substrate specificity, Biochemistry. 33:6936–6944.

    PubMed  CAS  Google Scholar 

  • McKay, G.A. and Wright, G.D., 1995, Kinetic mechanism of aminoglycoside phosphotransferase type IIIa: Evidence for a Theorell-Chance mechanism, J. Biol. Chem 270:24686–24692.

    PubMed  CAS  Google Scholar 

  • Menard, R., Molinas, C., Arthur, M., Duval, J., Courvalin, P. and Leclerq, R., 1993, Overproducion of 3′-amino-glycoside phosphotransferase type I confers resistance to tobramycin in Escherichia coli, Antimicrob. Agents Chemother 37:78–83.

    PubMed  CAS  Google Scholar 

  • Miller, G.H., Sabatelli, F.J., Hare, R.S., Glupczynski, Y., Mackey, P., Shlaes, D., Shimizu, K., Shaw, K.J. and Aminoglycoside Resistance Study Groups, 1997, The most frequent aminoglycoside resistance mechanisms-changes with time and geographic area: a reflection of aminoglycoside usage patterns?, Clin. Infect. Dis 24:S46–S62.

    PubMed  CAS  Google Scholar 

  • Miller, M.H., Edberg, S.C., Mandel, L.J., Behar, C.F. and Steigbigel, N.H., 1980, Gentamicin uptake in wild-type and aminoglycoside-resistant small-colony mutants of Staphylococcus aureus, Antimicrob. Agents Chemother 18:722–729.

    PubMed  CAS  Google Scholar 

  • Moazed, D. and Noller, H.F., 1987, Interaction of antibiotics with functional sites in 16S ribosomal RNA, Nature. 27:389–394.

    Google Scholar 

  • Morris, J.C. and Mensa-Wilmot, K., 1997, Role of 2,6-dideoxy-2,6-diaminoglucose in activation of a eukaryotic phospholipase C by aminoglycoside antibiotics, J. Biol. Chem 272:29554–29559.

    PubMed  CAS  Google Scholar 

  • Murphy, E., 1985, Nucleotide sequence of a spectinomycin adenyltransferase AAD(9) determinant from Staphylococcus aureus and its relationship to AAD(3″)(9), Mol. Gen. Genet 200:33–39.

    PubMed  CAS  Google Scholar 

  • Musser, J.M., 1995, Antimicrobial agent resistance in mycobacteria: molecular genetic insights, Clin. Microbiol. Rev 8:496–514.

    PubMed  CAS  Google Scholar 

  • Nagabhushan, T.L., Cooper, A.B., Tsai, H., Daniels, P.J. and Miller, G.H., 1978, The syntheses and biological properties of 1-N-(S-4-amino-2-hydroxybutyryl)-gentamicin B and 1-N-(S-3-amino-2-hydroxypropionyl)-gentamicin B, J. Antibiot 31:681–687.

    PubMed  CAS  Google Scholar 

  • Nassberger, L., Bergstrand, A. and DePierre, J.W., 1990, Intracellular distribution of gentamicin within the rat kidney cortex: a cell fractionation study, Exp. Mol. Pathol 52:212–220.

    PubMed  CAS  Google Scholar 

  • O’hara, K., Ohmiya, K. and Kono, M., 1988, Structure of adenylylated streptomycin synthesized enzymatically by Bacillus subtilis, Antimicrob. Agents Chemother 32:949–950.

    CAS  Google Scholar 

  • Ohmiya, K., Tanaka, T., Noguchi, N., O’Hara, K. and Kono, M., 1989, Nucleotide sequence of the chromosomal gene coding for the aminoglycoside 6-adenylyltransferase from Bacillus subtilis Marburg 168, Gene 78:377–378.

    PubMed  CAS  Google Scholar 

  • Ohta, T. and Hasegawa, M., 1993a, Analysis of the nucleotide sequence of fmrT encoding the self-defense gene of the istamycin producer, Streptomyces tenjimariensis ATCC 31602; comparison with the squences of kamB of Streptomyces tenebrarius NCIB 11028 and kamC of iCL102, J. Antibiot 46:511–517.

    PubMed  CAS  Google Scholar 

  • Ohta, T. and Hasegawa, M., 1993b, Analysis of the self-defense gene (fmrO) of a fortimicin A (astromicin) producer, Micromonospora olivasterospora: comparison with other aminoglycoside-resistance-encoding genes, Gene 127:63–69.

    PubMed  CAS  Google Scholar 

  • Oka, A., Sugisaki, H. and Takanami, M., 1981, Nucleotide sequence of the kanamycin resistance transposon Tn903, J. Mol Biol 147:217–226.

    PubMed  CAS  Google Scholar 

  • Ounissi, H. and Courvalin, P. (1987), Nucleotide sequences of streptococcal genes, in Streptococcal Genetics (J. J. Ferretti and R. Curtiss III, Eds.) pp 275, American Society for Microbiology, Washington, D.C.

    Google Scholar 

  • Owen, D.J., Noble, M.E., Garman, E.F., Papageorgiou, A.C. and Johnson, L.N., 1995, Two structures of the catalytic domain of Phosphorylase kinase: an active protein kinase complexed with substrate analogue and product, Structure. 3:467–482.

    PubMed  CAS  Google Scholar 

  • Pansegrau, W., Miele, L., Lurz, R. and Lanka, E., 1987, Nucleotide sequence of the kanamycin resistance determinant of plasmid RP4:Homology to other aminoglycoside 3′-phosphotransferases, Plasmid. 18:193–204.

    PubMed  CAS  Google Scholar 

  • Papadopoulou, B. and Courvalin, P., 1988, Dispersal in Campylobacter spp of aphA-3, a kanamycin resistance determinant from gram-positive cocci, Antimicrob. Agents Chemother 32:945–948.

    PubMed  CAS  Google Scholar 

  • Pardo, J.M., Malpartida, F., Rico, M. and Jimenez, A., 1985, Biochemical basis of resistance to hygromycin B in Streptomyces hygroscopicus—the producing organism, J. Gen. Microbiol 131:1289–1298.

    PubMed  CAS  Google Scholar 

  • Payie, K.G. and Clarke, A.J., 1997, Characterization of gentamicin 2′-N-acetyltransferase from Providencia stuar-tii: its use of peptidoglycan metabolites for acetylation of both aminoglycosides and peptidoglycan, J. Bacteriol 179:4106–4114.

    PubMed  CAS  Google Scholar 

  • Payie, K.G., Rather, P.N. and Clarke, A.J., 1995, Contribution of gentamicin 2′-N-acetyltransferase to the O-acety-lation of peptidoglycan in Providencia stuartii, J. Bacteriol 177:4303–4310.

    PubMed  CAS  Google Scholar 

  • Payie, K.G., Strating, H. and Clarke, A.J., 1996, The role of O-acetylation in the metabolism of peptidoglycan in Providencia stuartii, Microb. Drug Resist 2:135–140.

    PubMed  CAS  Google Scholar 

  • Perdersen, L.C., Benning, M.M. and Holden, H.M., 1995, Structural investigation of the antibiotic and ATP-bind-ing sites in kanamycin nucleotidyltransferase, Biochemsitry. 34:13305–13311.

    Google Scholar 

  • Piepersberg, W., Distler, J., Heinzel, P. and Perez-Gonzalez, J.-A., 1988, Antibiotic resistance by modification: many resistance genes could be derived from cellular control genes in actinomycetes.-A hypothesis, Actinomycetol 2:83–98.

    Google Scholar 

  • Piepersberg, W., Heinzel, P., Mansouri, K., Mönnighoff, U. and Pissowotzki, K. (1991), Evolution of antibiotic resistance and production genes in streptomycetes, in Genetics and product formation in Streptomyces (S. Baumberg, H. Krügel and D. Novack, Eds.), pp. 161–170, Plenum Press, New York.

    Google Scholar 

  • Priuska, E.M. and Schacht, J., 1995, Formation of free radicals by gentamycin and iron and evidence for an iron/gentamicin complex, Biochem. Pharmacol 50:1749.

    PubMed  CAS  Google Scholar 

  • Radika, K. and Northop, D.B., 1984a, Substrate specificities and structure-activity relationships for acylation of antibiotics catalyzed by kanamycin acetyltransferase, Biochemistry. 23:5118–5122.

    PubMed  CAS  Google Scholar 

  • Radika, K. and Northrop, D.B., 1984b, The kinetic mechanism of kanamycin acetyltransferase derived from the use of alternative antibiotics and coenzymes, J. Biol. Chem 259:12543–12546.

    PubMed  CAS  Google Scholar 

  • Radika, K. and Northrop, D., 1984c, Purification of two forms of kanamycin acetyltransferase from Escherichia coli, Arch. Biochem. Biophys 233:272–285.

    PubMed  CAS  Google Scholar 

  • Radika, K. and Northrop, D.B., 1984d, Correlation of antibiotic resistance with V max/K m ratio of enzymatic modification of aminoglycosides by kanamycin acetyl-transferase, Antimicrob. Agents Chemother 25:479–482.

    PubMed  CAS  Google Scholar 

  • Rao, R.N., Allen, N.E., Hobbs, J.N.J., Alborn, W.E.J., Kirst, H.A. and Paschal, J.W., 1983, Genetic and enzymatic basis of hygromycin B resistance in Escherichia coli, Antimicrob. Agents Chemother 24:689–695.

    PubMed  CAS  Google Scholar 

  • Rather, P.N., Mann, P.A., Mierzwa, R., Hare, R.S., Miller, G.H. and Shaw, K.J., 1993a, Analysis of the aac(3)-Vla gene encoding a novel 3-N-acetyltransferase, Antimicrob. Agents Chemother. 37:2074–2079.

    PubMed  CAS  Google Scholar 

  • Rather, P.N., Mierzwa, R., Hare, R., Miller, G. and Shaw, K., 1992a, Cloning and DNA sequence analysis of an aac(3)-Vb gene from Serratia marcescens, Antimicrob. Agents Chemother 36:2222–2227.

    PubMed  CAS  Google Scholar 

  • Rather, P.N., Munayyer, H., Mann, P.A., Hare, R.S., Miller, G.H. and Shaw, K.J., 1992b, Genetic analysis of bacterial acetyltransferases: Identification of amino acids determining the specificities of the aminoglycoside 6′-N-acetyltransferase lb and IIa proteins, J. Bacteriol 175:3196–3203.

    Google Scholar 

  • Rather, P.N. and Orosz, E., 1994, Characterization of aar A, a pleiotrophic negative regulator of the 2′-N-acetyl-transferase in Providencia stuartii, J. Bacteriol 176:5140–5144.

    PubMed  CAS  Google Scholar 

  • Rather, P.N., Orosz, E., Shaw, K.J., Hare, R. and Miller, G., 1993b, Characterization and transcriptional regulation of the 2′-N-acetytransferase gene from Providencia stuartii, J. Bacteriol 175:6492–6498.

    PubMed  CAS  Google Scholar 

  • Rather, P.N., Parojcic, M.M. and Paradise, M.R., 1997a, An extracellular factor regulating expression of the chromosomal aminoglycoside 2′-N-acetyltransferase of Providencia stuartii, Antimicrob. Agents Chemother 41:1749–1754.

    PubMed  CAS  Google Scholar 

  • Rather, P.N., Solinsky, K., A., Paradise, M.R. and Parojcic, M.M., 1997b, aarC, an essential gene involved in density-dependent regulation of the 2′-N-acetyltransferase in Providentia stuartii, J. Bacteriol 179:2267–2273.

    PubMed  CAS  Google Scholar 

  • Roestamadji, J., Grapsas, I. and Mobashery, S., 1995a, Loss of individual electrostatic interactions between aminoglycoside antibiotics and resistance enzymes as an effective means to overcoming bacterial drug resistance, J. Am. Chem. Soc 117:11060–11069.

    CAS  Google Scholar 

  • Roestamadji, J., Grapsas, I. and Mobashery, S., 1995b, Mechanism-based inactivation of bacterial aminoglycoside 3′-phosphotransferases, J. Am. Chem. Soc 117:80–84.

    CAS  Google Scholar 

  • Rouch, D.A., Byrne, M.E., Kong, Y.C. and Skurray, R.A., 1987, The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus: Expression and nucleotide sequence analysis, J. Gen. Microbiol 133:3039–3052.

    PubMed  CAS  Google Scholar 

  • Sakon, J., Liao, H.H., Kanikula, A.M., Benning, M.M., Rayment, I. and Holden, H.M., 1993, Molecular structure of kanamycin nucleotidyl transferase determind to 3Å resolution, Biochemistry. 32:11977–11984.

    PubMed  CAS  Google Scholar 

  • Salauze, D. and Davies, J., 1991a, Isolation and characterization of and aminoglycoside phosphotransferase from neomycin-producing Micromonospora chalcea: Comparison with that of Streptomyces fradiae and other producers of 4,6-disubstituted 3-deoxystreptamine antibiotics, J. Antibiot 44:1432–1443.

    PubMed  CAS  Google Scholar 

  • Salauze, D., Perez-Gonzalez, J.-A., Piepersberg, W. and Davies, J., 1991b, Characterization of aminoglycoside acetyltransferase-encoding genes of neomycin-producing Micromonospora chalcea and Streptomyces fradiae, Gene 101:143–148.

    PubMed  CAS  Google Scholar 

  • Sanders, T.W.J., Reinhard, M.K., Jollow, D.J. and Hottendorf, G.H., 1993, Lack of in vivo evidence of a cytochrome P450 metabolite participating in aminoglycoside nephrotoxicity, Biochem. Pharmacol 45:780–782.

    PubMed  CAS  Google Scholar 

  • Sarwar, M. and Akhtar, M., 1990, Cloning of aminoglycoside phosphotransferase (APH) gene from antibiotic-producing strain of Bacillus circulans into a high-expression vector, pKK223—3. Purification, properties and location of the enzyme, Biochem. J 268:671–677.

    PubMed  CAS  Google Scholar 

  • Sawaya, M.R., Pelletier, H., Kumar, A., Wilson, S.H. and Kraut, J., 1994, Crystal structure of rat DNA polymerase β: evidence for a common polymerase mechanism, Science. 264:1930–1935.

    PubMed  CAS  Google Scholar 

  • Schacht, J., 1993, Biochemical basis of aminoglycoside ototoxicity, Otolaryngol. Clin. North. Am 26:845–856.

    PubMed  CAS  Google Scholar 

  • Schatz, A., Bugie, E. and Waksman, S.A., 1944, Streptomycin, a substance exibiting antibiotic activity against Gram-positive and Gram-negative bacteria, Proc. Soc. Exp. Biol. Med 55(66–69).

    CAS  Google Scholar 

  • Schlessinger, D., 1988, Failure of aminoglycoside antibiotics to kill anaerobic, low-pH, and resistant cultures, Clin. Microbiol. Rev 1:54–59.

    PubMed  CAS  Google Scholar 

  • Schmidt, F.R., Nucken, E.J. and Henschke, R.B., 1988, Nucleotide sequence analysis of 2″-aminoglycoside nucleotidyl-transferase ANT(2″) from Tn4000: its relationship with AAD(3″) and impact on Tn21 evolution, Mol. Microbiol 2:709–111.

    PubMed  CAS  Google Scholar 

  • Scholz, P., Haring, V., Wittmann-Liebold, B., Ashman, K., Bagdasarian, M. and Scherzinger, E., 1989, Complete nucleotide sequence and gene organization of the broad-host-range plasmid RSF1010, Gene 75(271–288).

    PubMed  CAS  Google Scholar 

  • Schwocho, L.R., Schaffner, C.P., Miller, G.H., Hare, R.S. and Shaw, K.J., 1995, Cloning and characterization of a 3-N-aminoglycoside acetyltransferase gene, aac(3)-Ib, from Pseudomonas aeruginosa, Antimicrob. Agents Chemother 39:1790–1796.

    PubMed  CAS  Google Scholar 

  • Shaw, K.J., 1997, Personal communication.

    Google Scholar 

  • Shaw, K.J., Cramer, C.A., Rizzo, M., Mierzwa, R., Gewain, K., Miller, G.H. and Hare, R.S., 1989, Isolation, characterization, and DNA sequence analysis of an AAC(6′)-II gene from Pseudomonas aeruginosa, Antimicrob. Agents Chemother 33:2052–2062.

    PubMed  CAS  Google Scholar 

  • Shaw, K.J., Gomez-Lus, S. and Shannon, K.W., 1992a, unpublished sequence, GenBank accession no. L06160.

    Google Scholar 

  • Shaw, K.J. and Leal, I., 1992, unpublished sequence GenBank accession no. L06161.

    Google Scholar 

  • Shaw, K.J., Rather, P.N., Sabatelli, F.J., Mann, P., Munayyer, H., Mierzwa, R., Petrikkos, G.L., Hare, R.S., Miller, G.H., Bennett, P. and Downey, P., 1992b, Characterization of the chromosomal aac(6′)-Ic gene from Serratia marcescens, Antimicrob. Agents Chemother 36:1447–1455.

    PubMed  CAS  Google Scholar 

  • Shaw, K.J., Rather, P.N., Hare, R.S. and Miller, G.H., 1993, Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes, Microbiol. Rev 57:138–163.

    PubMed  CAS  Google Scholar 

  • Shomura, T., Ezaki, N., Tsuruoka, T., Niwa, T., Akita, E. and Niida, T., 1970, Studies on antibiotic SF-733, a new antibiotic. I. Taxonomy, isolation and characterization, J. Antibiot 23:155–161.

    PubMed  CAS  Google Scholar 

  • Sigmund, C.D., Ettayebi, M. and Morgan, E.A., 1984, Antibiotic resistance mutations in 16S and 23S ribosomal RNA genes of Escherichia coli, Nucleic Acids Res 12:4653–4663.

    PubMed  CAS  Google Scholar 

  • Siregar, J.J., Lerner, S.A. and Mobashery, S., 1994, Purification and characterization of aminoglycoside 3′-phos-photransferase Type IIa and kinetic comparison with a new mutant enzyme, Antimicrob. Agents Chemother 38:641–647.

    PubMed  CAS  Google Scholar 

  • Siregar, J.J., Miroshnikov, K. and Mobashery, S., 1995, Purification, characterization, and investigation of the mechanism of aminoglycoside 3′-phosphotransferase Type la, Biochemistiy 34:12681–12688.

    CAS  Google Scholar 

  • Skeggs, P.A., Holmes, D.J. and Cundliffe, E., 1987, Cloning of aminoglycoside-resistance determinants from Streptomyces tenebrarius and comparison with related genes from other actinomycetes, J. Gen. Microbiol 133:915–923.

    PubMed  CAS  Google Scholar 

  • Song, B.B. and Schacht, J., 1996, Variable efficacy of radical scavengers and iron chelators to attenuate gentami-cin ototoxicity in guinea pig in vivo, Hearing Res 94:87.

    CAS  Google Scholar 

  • Sundin, G.W. and Bender, C.L., 1996, Dissemination of the strA-strB streptomycin-resistance genes among commensal and pathogenic bacteria fromhumans, animals, and plants, Mol. Ecol 5:133–143.

    PubMed  CAS  Google Scholar 

  • Suter, T.M., Viswanathan, V.K. and Cianciotto, N.P., 1997, Isolation of a gene encoding a novel spectinomycin phosphotransferase from Legionella pneumophila, Antimicrob. Agents Chemother. 41:1385–1388.

    PubMed  CAS  Google Scholar 

  • Sutherland, R., 1991, β-Lactamase inhibitors and reversal of antibiotic resistance, Trends Pharmacol. Sci 12:227–232.

    PubMed  Google Scholar 

  • Taber, H.W., Mueller, J.P., Miller, P.F. and Arrow, A.S., 1987, Bacterial uptake of aminoglycoside antibiotics, Microbiol. Rev 51:439–457.

    PubMed  CAS  Google Scholar 

  • Tanaka, N., Matsunaga, K., Yamaki, H. and Nishimura, T., 1984, Inhibition of initiation of DNA synthesis by aminoglycoside antibiotics, Biochem. Biophys. Res. Commun 122:460–465.

    PubMed  CAS  Google Scholar 

  • Tangy, F., Capmau, M.-L. and Le Goffic, F., 1983, Photo-induced labelling of Escherichia coli ribosomes by a tobramycin analog, Eur. J. Biochem 131:581–587.

    PubMed  CAS  Google Scholar 

  • Taylor, D.E., Yan, W., Ng, L.K., Manavathu, E.K. and Courvalin, P., 1988, Genetic characterization of kanamycin resistance in Campylobacter coli, Ann. Inst. Pasteur Microbiol 139:665–676.

    PubMed  CAS  Google Scholar 

  • Taylor, S.S., Knighton, D.R., Zheng, J., Ten Eyck, L.F. and Sowadski, J.M., 1992, Structural framework for the protein kinase family, Annu. Rev. Cell Biol 8:429–62.

    PubMed  CAS  Google Scholar 

  • Tenover, F.C., Filpula, D., Phillips, K.L. and Plorde, J.J., 1988, Cloning and sequencing of a gene encoding an aminoglycoside 6′-N-acetyltransferase from an R factor of Citrobacter diversus, J. Bacteriol 170:471–473.

    PubMed  CAS  Google Scholar 

  • Tenover, F.C., Gilbert, T. and O’Hara, P., 1988, Nucleotide sequence of a novel kanamycin resistance gene, aphA-7, from Campylobacter jejuni and comparison to other kanamycin phosphotransferase genes, Plasmid 22:52–58.

    Google Scholar 

  • Tenover, F.C., Phillips, K.L., Gilbert, T., Lockhart, P., O’Hara, P.J. and Plorde, J.J., 1989, Development of a DNA probe from the deoxyribonucleotide sequence of a 3-N-aminoglycoside acetyltransferase [AAC(3)-I] resistance gene, Antimicrob. Agents Chemother 33:551–559.

    PubMed  CAS  Google Scholar 

  • Terán, F.J., Suárez, J.E. and Mendoza, M.C., 1991, Cloning, sequencing, and use as a molecular probe of a gene encoding an aminoglycoside 6′-N-acetyltransferase of broad substrate profile, Antimicrob. Agents Chemother 35:714–719.

    PubMed  Google Scholar 

  • Thal, L.A., Chow, J.W., Patterson, J.E., Petri, M.B., Donabedian, S., Clewell, D.B. and Zervos, M.J., 1993, Molecular characterization of highly gentamicin-resistant Enterococcus faecalis isolates lacking high-level streptomycin resistance, Antimicrob. Agents Chemother 37:134–137.

    PubMed  CAS  Google Scholar 

  • Thompson, C.J. and Gray, G.S., 1993, Nucleotide sequence of a streptomycete aminoglycoside phosphotransferase gene and its relationship to phosphotransferases encoded by resistance plasmids, Proc. Natl. Acad. Sci. USA 80:5190–5194.

    Google Scholar 

  • Thompson, C.J., Ward, J.M. and Hopwood, D.A., 1980, DNA cloning in Streptomyces: resistance genes from antibiotic-producing species, Nature. 286:525–527.

    PubMed  CAS  Google Scholar 

  • Thompson, J., Skeggs, P.A. and Cundliffe, E., 1985, Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Mi-cromonospora purpurea. Mol. Gen. Genet 201:168–173.

    PubMed  CAS  Google Scholar 

  • Thompson, P.R., Hughes, D.W. and Wright, G.D., 1996a, Mechanism of aminoglycoside 3′-phosphotransferase type IIIa: Hisl88 is not a phosphate-accepting-residue, Chem. Biol 3:747–755.

    PubMed  CAS  Google Scholar 

  • Thompson, P.R., Hughes, D.W. and Wright, G.D., 1996b, Regiospecificity of aminoglycoside phosphotransferase from Enterococci and Staphylococci (APH(3′)-IIIa), Biochemistry. 35:8686–8695.

    PubMed  CAS  Google Scholar 

  • Tran van Nhieu, G. and Collatz, E., 1987, Primary structure of an aminoglycoside 6′-N-acetyltransferase AAC(6′)-4, fused in vivo with the signal peptide of the Tn3-encoded $-lactamase, J. Bacteriol 169:5708–5714.

    Google Scholar 

  • Trieu-Cuot, P. and Courvalin, P., 1983, Nucleotide sequence of the Streptococcus faecalis plasmid gene encoding the 3′5″-aminoglycoside phosphotransferase type III, Gene 23:331–341.

    PubMed  CAS  Google Scholar 

  • Ubukata, K., Yamashita, N., Gotoh, A. and Konno, M., 1984, Purification and characterization of aminoglycoside-modifying enzymes from Staphylococcus aureus and Staphylococcus epidermidis, Antimicrob. Agents Chemother 25:754–759.

    PubMed  CAS  Google Scholar 

  • Umezawa, H., Nishimura, Y., Tsuchiya, T. and Umezawa, S., 1972, Syntheses of 6′-N-methyl-kanamycin and 3′,4′-dideoxy-6′-N-methylkanamycin B active against resistant strains having 6′-N-acetylating enzymes, J. Antibiot 25:743–745.

    PubMed  CAS  Google Scholar 

  • Umezawa, H., Ueda, M., Maeda, K., Yagishita, K., Kando, S., Okami, Y., Utahara, R., Osato, Y., Nitta, K. and Kakeuchi, T., 1957, Production and isolation of a new antibiotic kanamycin, J. Antibiot 10:181–189.

    PubMed  CAS  Google Scholar 

  • Vakulenko, S.B. and Entina, E.G., 1990, Nucleotide sequence of aacC2 gene from a clinical strain of Escherichia coli, Antibiot. Khimioter 35:46–50.

    PubMed  CAS  Google Scholar 

  • Van Pelt, J.E., Iyengar, R. and Frey, P.A., 1986, Gentamicin nucleotidyltransferase. Stereochemical inversion at phosphorus in enzymatic 2′-deoxyadenylyl transfer to tobramycin, J. Biol. Chem 261:15995–15999.

    PubMed  Google Scholar 

  • Van Pelt, J.E. and Northrop, D.B., 1984, Purification and properties of gentamicin nucleotidyltransferase from Escherichia coli: Nucleotide specificity, pH optimum, and the separation of two electrophoretic variants, Arch. Biochem. Biophys 230:250–263.

    PubMed  Google Scholar 

  • Van Pelt, J.E., Mooberry, E.S. and Frey, P.A., 1990, 1H 13C, and 31P Nuclear magnetic resonance spectral assignments for tobramycin, 2″-(adenosine-5′-phosphoryl)-tobramycin and 2″-(adenosine-5′-thiophosphoryl)-to-bramycin, Arch. Biochem. Biophys 280:284–291.

    PubMed  Google Scholar 

  • Vliegenthart, J.S., Ketelaar-Van Gaalen, P.A. and van de Klundert, J.A., 1989, Nucleotide sequence of the aacC2 gene, a gentamicin resistance determinant involved in a hospital epidemic of multiply resistant members of the family Enterobacteriaceae, Antimicrob. Agents Chemother 33:1153–1159.

    PubMed  CAS  Google Scholar 

  • Vliegenthart, J.S., Ketelaar-van Gaalen, P.A. and van de Klundert, J.A., 1991, Nucleotide sequence of the aacC3 gene, a gentamicin resistance determinant encoding aminoglycoside-(3)-N-acetyltransferase III expressed in Pseudomonas aeruginosa but not in Escherichia coli, Antimicrob. Agents Chemother 35:892–897.

    PubMed  CAS  Google Scholar 

  • Vögtli, M. and Hütter, R., 1987, Characterisation of the hydroxy streptomycin phosphotransferase gene (sph) of Streptomyces glaucescens: nucleotide sequence and promoter analysis, Mol. Gen. Genet 208:195–203.

    PubMed  Google Scholar 

  • Waksman, S.A. and Lechevalier, H.A., 1949, Neomycin, a new antibiotic active against streptomycin-resistant bacteria, including tuberculosis organisms, Science. 109:305–307.

    PubMed  CAS  Google Scholar 

  • Wang, Y., Hamasaki, K. and Rando, R.R., 1997, Specificity of aminoglycoside binding to RNA constructs derived from the 16S rRNA deconding region an the HIV-RRE activator region, Biochemistry. 36:768–779.

    PubMed  CAS  Google Scholar 

  • Weinstein, M.J., Luedemann, G.M., Oden, E.M., Wagman, G.H., Rosselet, J.P., Marquez, J.A., Coniglio, C.T., Charney, W., Herzog, H.L. and Black, J.., 1963, Gentamicin, a new antibiotic complex from Micromono-spora, J. Med. Chem 6:463–464.

    PubMed  CAS  Google Scholar 

  • Weinstein, M.J., Marquez, J.A., Testa, R.T., Wagman, G.H., Oden, E.M. and Waitz, J.A., 1970, Antibiotic 6640, a new Micromonospora-produced aminoglycoside antibiotic, J. Antibiotic 23:551–554.

    CAS  Google Scholar 

  • Werstuck, G., Zapp, M.L. and Green, M.R., 1996, A non-canonical base pair within the human immunodificiency virus Rev-responsive element is involved in both Rev and small molecule recognition, Chem. Biol 3:129–137.

    PubMed  CAS  Google Scholar 

  • Williams, J.W. and Northrop, D.B., 1976, Purification and properties of gentamincin acetyltransferase I, Biochemistry. 15:125–131.

    PubMed  CAS  Google Scholar 

  • Williams, J.W. and Northrop, D.B., 1978a, Kinetic mechanism of gentamicin acetyltransferase I, J. Biol. Chem 253:5902–5907.

    PubMed  CAS  Google Scholar 

  • Williams, J.W. and Northrop, D.B., 1978b, Substrate specificity and structure-activity relationships of gentamicin acetyltransferase I, J. Biol. Chem 253:5908–5914.

    PubMed  CAS  Google Scholar 

  • Williams, J.W. and Northrup, D.B., 1979, Synthesis of a tight-binding, multisubstrate analog inhibitor of gentamicin acetyltransferase, J. Antibiot 32:1147–1154.

    PubMed  CAS  Google Scholar 

  • Woo, P.W.K., Dion, H.W. and Bartz, Q.R., 1971, Butirosins A and B, aminoglycoside antibiotics. I. Structural units. Tet. Lett: 2617–2620.

    Google Scholar 

  • Woodcock, J., Moazed, D., Cannon, M., Davies, J. and Noller, H.F., 1991, Interaction of antibiotics with A-and P-site-specific bases in 16S ribosomal RNA, EMBO J 10:3099–3103.

    PubMed  CAS  Google Scholar 

  • Wright, G.D. and Ladak, P., 1997, Overexpression and characterization of the chromosomal aminoglycoside 6′-N-acetyltransferase from Enterococcus faecium, Antimicrob. Agents Chemother 41:956–960.

    PubMed  CAS  Google Scholar 

  • Wu, H.Y., Miller, G.H., Guzman Blanco, M., Hare, R.S. and Shaw, K.J., 1997, Cloning and characterization of an aminoglycoside 6′-N-acetyltransferase gene from Citrobacter freundii which confers an altered resistance profile, Antimicrob. Agents Chemother 41:2439–2447.

    PubMed  CAS  Google Scholar 

  • Xu, R.-M., Carmel, G., Kuret, J. and Cheng, X., 1996, Structural basis for selectivity of the isoquinoline sulfonamide family of protein kinase inhibitors, Proc. Natl. Acad. Sci. USA 93:6308–6313.

    PubMed  CAS  Google Scholar 

  • Yenofsky, R.L., Fine, M. and Pellow, J.W., 1990, A mutant neomycin phosphotransferase II gene reduces the resistance of transformants to antibiotic selection pressure, Proc. Natl. Acad. Sci. USA 87:3435–3439.

    PubMed  CAS  Google Scholar 

  • Young, M.L., Bains, M., Bell, A. and Hancock, R.E., 1992, Role of Pseudomonas aeruginosa outer membrane protein OprH in polymyxin and gentamicin resistance: isolation of an OprH-deficient mutant by gene replacement techniques, Antimicrob. Agents Chemother 36:2566–2568.

    PubMed  CAS  Google Scholar 

  • Zalacain, M., Gonzalez, A., Guerrero, M.C., Mattaliano, R.J., Malpartida, F. and Jimenez, A., 1986, Nucleotide sequence of the hygromycin B phosphotransferase gene from Streptomyces hygroscopicus, Nucleic Acids Res 14:1565–1581.

    PubMed  CAS  Google Scholar 

  • Zalacain, M., Malpartida, F., Pulido, D. and Jimenez, A., 1987a, Cloning and expression in Escherichia coli of a hygromycin B phosphotransferase gene from Streptomyces hygroscopicus, Eur. J. Biochem. 162:413–418.

    PubMed  CAS  Google Scholar 

  • Zalacain, M., Pardo, J.M. and Jimenez, A., 1987b, Purification and characterization of a hygromycin B phosphotransferase from Streptomyces hygroscopicus, Eur. J. Biochem 162:419–422.

    PubMed  CAS  Google Scholar 

  • Zapp, M.L., Stern, S. and Green, M.R., 1993, Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production, Cell 74:969–978.

    PubMed  CAS  Google Scholar 

  • Zhang, C.-C., 1996, Bacterial signalling involving eukaryotic-type protein kinases, Mol Microbiol 20:9–15.

    PubMed  Google Scholar 

  • Zhang, F., Strand, A., Robbins, D., Cobb, M.H. and Goldsmith, E.J., 1994, Atomic structure of the MAP kinase ERK2 at 2.3 Å resolution, Nature 367:704–11.

    PubMed  CAS  Google Scholar 

  • Zhou, J. and Adams, J.A., 1997, Is there a catalytic base in the active site of cAMP-dependent protein kinase? Biochemistry. 36:2977–2984.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada

    Gerard D. Wright & Albert M. Berghuis

  2. Department of Chemistry, Wayne State University, Detroit, Michigan, 48202, USA

    Shahriar Mobashery

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  1. Gerard D. Wright
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  2. Albert M. Berghuis
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  1. Wayne State University, Detroit, Michigan, USA

    Barry P. Rosen  & Shahriar Mobashery  & 

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Wright, G.D., Berghuis, A.M., Mobashery, S. (1998). Aminoglycoside Antibiotics. In: Rosen, B.P., Mobashery, S. (eds) Resolving the Antibiotic Paradox. Advances in Experimental Medicine and Biology, vol 456. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4897-3_4

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  • DOI: https://doi.org/10.1007/978-1-4615-4897-3_4

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