Advertisement

How β-Lactamases Have Driven Pharmaceutical Drug Discovery

From Mechanistic Knowledge to Clinical Circumvention
  • Karen Bush
  • Shahriar Mobashery
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 456)

Abstract

Although antibiotic resistance has only recently become a recognized topic for the popular press, resistance has been the major stimulus for the pharmaceutical development of novel β-lactam antibiotics. Benzylpenicillin (Penicillin G), the first member of this important class of antibacterial agents, was initially used to counteract Gram-positive infections, particularly those caused by Streptococcus pneumoniae, the scourge of hospitals in the 1940s. Before penicillins found widespread clinical utility, it was discovered that certain bacterial enzymes, the β-lactamases, had the ability to hydrolyze the lactam ring of these antibiotics and render them ineffective as antibacterial agents (Abraham and Chain, 1940; Kirby, 1944). When resistance to penicillin was soon selected rapidly by β-lactamase-producing bacteria, it became obvious that the hydrolytic β-lactamases could potentially destroy the utility of this potent class of antibiotics. The pharmaceutical industry has proceeded to identify novel β-lactams over the past 40 years in an attempt to keep ahead of the continuous evolution of new β-lactamases with altered hydrolytic properties. Two approaches were undertaken: development of agents stable to hydrolysis by the major β-lactamases, and identification of potent inhibitors for these enzymes. The topics germane to these strategies will be addressed in this manuscript.

Keywords

Clavulanic Acid Hydrolytic Water C1avulanic Acid Transpeptidation Reaction Renal Dipeptidase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abraham, E.P., and Chain, E., 1940, An enzyme from bacteria able to destroy penicillin, Nature, 146:837.CrossRefGoogle Scholar
  2. Aharonowitz, Y., and Cohen, G., 1992, Penicillin and cephalosporin biosynthetic genes: structure, organization, regulation, and evolution, Ann. Rev. Microbiol, 46:461.CrossRefGoogle Scholar
  3. Ambler, R.P., 1980, The structure of β-lactamases, Philos. Trans. R. Soc. Lond. [Biol], 289:321.CrossRefGoogle Scholar
  4. Baggaley, K.H., Brown, A.G., and Schofield, C.J., 1997, Chemistry and biosynthesis of clavulanic acid and other clavams, Nat. Prod. Rep, 14:309.PubMedCrossRefGoogle Scholar
  5. Bandoh, K., Watanabe, K., Muto, Y., Tanaka, Y., Kato, N., and Ueno, K., 1992, Conjugal transfer of imipenem resistance in Bacteroides fragilis, J. Antibiot. (Tokyo), 45:542.CrossRefGoogle Scholar
  6. Belaaouaj, A., Lapoumeroulie, C., Canica, M.M., Vedel, G., Nevot, P., Krishnamoorthy, R., and Paul, G., 1994, Nucleotide sequences of the genes coding for the TEM-like beta-lactamases IRT-1 and IRT-2 (formerly called TRI-1 and TRI-2), FEMS Microbiol. Lett, 120:75.PubMedGoogle Scholar
  7. Berger-Baechi, B., 1995, Factors affecting methicillin resistance in Staphylococcus aureus, Int. J. Antimicrob. Agents, 6:13.CrossRefGoogle Scholar
  8. Birnbaum, J., Kahan, F.M., Kropp, H., and MacDonald, J.S., 1985, Carbapenems, a new class of beta-lactam antibiotics, The Amer. J. Med, 78 (suppl. 6A):3.CrossRefGoogle Scholar
  9. Blumberg, H. M., Rimland, D., Carroll, D. J., Terry, P., and Wachsmuth, I. K., 1991, Rapid development of ciprofloxacin resistance in methicillin-susceptible and resistant Staphylococcus aureus, J. Infect. Dis, 163:1279.PubMedCrossRefGoogle Scholar
  10. Bonomo, R. A., Dawes, C. G., Knox, J.R., and Shlaes, D. M., 1995, Complementary roles of mutations at positions 69 and 242 in class A β-lactamases, Biochim. Biophys. Acta, 1247:121.PubMedCrossRefGoogle Scholar
  11. Bounaga, S., Laws, A.P., Galleni, M., and Page, M.I., 1998, The mechanism of catalysis and the inhibition of the Bacillus cereus zinc-dependent β-lactamase, Biochem. J, 331(Pt 3):703.PubMedGoogle Scholar
  12. Brown, A.G., Butterworth, D., Cole, M., Hanscomb, G., Hood, J.D., Reading, C., and Rolinson, G.N., 1976, Naturally occuring β-lactamase inhibitors with antibacterial activity, J. Antibiot, 29:668.PubMedCrossRefGoogle Scholar
  13. Brown, R.P., Alpin, R.T., and Schofield, C.J., 1996, Inhibition of TEM-2 β-lactamase from Escherichia coli by clavulanic acid: observation of intermediates by electrospray ionisation mass spectrometry, Biochemistry, 35:12421.PubMedCrossRefGoogle Scholar
  14. Brown, R.P., Alpin, R.T., and Schofield, C.J., 1997, Mass spectrometric studies on the inhibition of TEM-2 β-lactamase by clavulanic acid derivatives, J. Antibiot, 50:184.PubMedCrossRefGoogle Scholar
  15. Buckley, M.M., Brogden, R.N., Barradel, L.B., and Goa, K.L., 1992, Imipenem/ cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy, Drugs, 44:408.PubMedCrossRefGoogle Scholar
  16. Bulychev, A., Massova, I., Miyashita, K., and Mobashery, S., 1997, Evolution of the versatile β-lactam hydrolase activity: from biosynthetic enzymes to drug resistance factors, J. Am. Chem. Soc, 119:7619.CrossRefGoogle Scholar
  17. Bush, K., 1989, Characterization of β-lactamases, Antimicrob. Agents Chemother, 33:259.PubMedCrossRefGoogle Scholar
  18. Bush, K., Bonner, D.P., and Sykes, R.B., 1980, Izumenolide—a novel beta-lactamase inhibitor produced by Micro-monospora, J. Antibiotics, 33:1262.CrossRefGoogle Scholar
  19. Bush, K., Jacoby, G.A., and Medeiros, A.A., 1995, A functional classification scheme for β-lactamases and its correlation with molecular structure, Antimicrob. Agents Chemother, 39:1211.PubMedCrossRefGoogle Scholar
  20. Bush, K., Macalintal, C., Rasmussen, B.A., Lee, V.J., and Yang, Y., 1993, Kinetic interactions of tazobactam with β-lactamases from all major structural classes, Antimicrob. Agents Chemother, 37:851.PubMedCrossRefGoogle Scholar
  21. Bush, K., and Singer, S.B., 1989, Biochemical characteristics of extended broad spectrum β-lactamases, Infection, 17:429.PubMedCrossRefGoogle Scholar
  22. Bush, K., Smith, S.A., Ohringer, S., Tanaka, S.K., and Bonner, D.P., 1987, Improved sensitivity in assays for binding of novel beta-lactam antibiotics to penicillin-binding proteins of Escherichia coli, Antimicrob. Agents Chemother, 31:1271.PubMedCrossRefGoogle Scholar
  23. Bush, K., and Sykes, R.B. 1987. Characterization and epidemiology of beta-lactamases, in: The Antimicrobial Agents Annual, Peterson P.K. and Verhoef J., eds., Elsevier, Amsterdam, p 371–382.Google Scholar
  24. Bush, K., Tanaka, S.K., Bonner, D.P., and Sykes, R.B., 1985, Resistance caused by decreased penetration of β-lactam antibiotics into Enterobacter cloacae, Antimicrob. Agents Chemother, 27:555.PubMedCrossRefGoogle Scholar
  25. Butterworth, D., Cole, M., Hanscomb, G., and Rolinson, G.N. 1979, Olivanic acids, a family of beta-lactam antibiotics with beta-lactamase inhibitory properties produced by Streptomyces species. I. Detection, properties and fermentation studies., J. Antibiotics, 32:287.CrossRefGoogle Scholar
  26. Carfi, A., Pares, S., Duee, E., Galleni, M., Duez, C., Frere, J.-M., and Dideberg, O., 1995, The 3-D structure of a zinc metallo-β-lactamase from Bacillus cereus reveals a new type of protein fold, EMBO, 14:4914.Google Scholar
  27. Charnas, R.L., and Knowles, J.R., 1981, Inhibition of the RTEM β-lactamase from Escherichia coli Interaction of enzyme with derivatives of olivanic acid, Biochemistry, 20:2732.PubMedCrossRefGoogle Scholar
  28. Charnas, R.L., Fisher, J., and Knowles, J.R., 1978, Chemical studies on the inactivation of Escherichia coli RTEM β-lactamase by clavulanic acid, Biochemistry, 17:2185.PubMedCrossRefGoogle Scholar
  29. Coffey, T.J., Dowson, C.G., Daniels, M., and Spratt, B.G., 1995, Genetics and molecular biology of β-lactam-re-sistant pneumococci, Microb. Drug Resist, 1:29.PubMedCrossRefGoogle Scholar
  30. Concha, N.O., Rasmussen, B.A., Bush, K., and Herzberg, O., 1996, Crystal structure of the wide-spectrum binu-clear zinc β-lactamase from Bacteroides fragilis, Structure, 4:823.PubMedCrossRefGoogle Scholar
  31. Condra, J. H., Schleif, W. A., Blahy, O. M., Gabryelski, L. J., Graham, D. J., Quintero, J. C, Rhodes, A., Robbins, H. L., Roth, E., Shivaprakash, M., Titus, D., Yang, T., Teppler, H., Squires, K. E., Deutsch, P. J., and Emini, E. A., 1995, In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors, Nature, 374:569.PubMedCrossRefGoogle Scholar
  32. Coronado, V. G., Edwards, J. R., Culver, D. H., and Gaynes, R. P., 1995, National nosocomial infections surveillance system, ciprofloxacin resistance among nosocomial Pseudomonas aeruginosa and Staphylococcus aureus in the United States. Infect. Control Hosp. Epidemiol 16:71.PubMedCrossRefGoogle Scholar
  33. D’Amato, C., Armignacco, O., Antonucci, G., Bordi, E., Bove, G., Decarli, G., De Mori, P., Rosci, M.A., and Visco, G., 1990, The efficacy and safety of imipenem/cilastatin in the treatment of severe bacterial infection, J. Chemother, 2:100.PubMedGoogle Scholar
  34. Datta, N., and Kontomichalou, P., 1965, Penicillinase synthesis controlled by infectious R factors in enterobacte-riaceae, Nature, 208:239.PubMedCrossRefGoogle Scholar
  35. Datta, N., and Richmond, M.H., 1966, The purification and properties of a penicillinase whose synthesis is mediated by an R-factor in Escherichia coli, Biochem. J, 98:204.PubMedGoogle Scholar
  36. Doran, J.L., Leskiw, B.K., Aippersbach, S., and Jensen, S.E., 1990, Isolation and characterization of a β-lac-tamase-inhibitory protein from streptomyces clavuligerus and cloning and analysis of the corresponding gene, J. Bacteriol, 172:4909.PubMedGoogle Scholar
  37. Dubus, A., Ledent, P., Lamotte-Brasseur, J., and Frère, J.M., 1996, The roles of residues Tyr150, Glu272, and His314 in class C β-lactamases, Proteins Struc. Func. Gen, 25:473.Google Scholar
  38. Dubus, A., Normark, S., Kania, M., and Page, M.G.P., 1994, The role of tyrosine 150 in catalysis of β-lactam hydrolysis by AmpC beta-lactamase from Escherichia coli investigated by site-directed mutagenesis, Biochemistry, 33:8577.PubMedCrossRefGoogle Scholar
  39. Dumon, L., Adriaens, P., Anne, J., and Eyssen, H., 1979, Effect of clavulanic acid on the minimum inhibitory concentration of benzylpenicillin, ampicillin, carbenicillin, or cephalothin against clinical isolates resistant to beta-lactam antibiotics, Antimicrob. Agents Chemother, 15:315.PubMedCrossRefGoogle Scholar
  40. Durckheimer, W., Blumbach, J., Lattrell, R., and Scheunemann, K.H., 1985, Recent developments in the field of beta-lactam antibiotics, Angew. Chem. Int. Ed. Engl, 24:180.CrossRefGoogle Scholar
  41. Easton, C.J., and Knowles, J.R., 1982, Inhibition of the RTEM β-lactamase from Escherichia coli Interaction of the enzyme with derivatives of olivanic acid, Biochemistry, 21:2857.PubMedCrossRefGoogle Scholar
  42. Edwards, J.R., Turner, P.J., Wannop, C., Withnell, E.S., Grindey, A.J., and Nairn, K., 1989, In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I., Antimicrob. Agents Chemother, 33:215.PubMedCrossRefGoogle Scholar
  43. Ellerby, L.M., Escobar, W.A., Fink, A.L., Mitchinson, C., and Wells, J., 1990, The role of lysine-234 in β-lactamase catalysis probed by site-directed mutagenesis, Biochemistry, 29:5797.PubMedCrossRefGoogle Scholar
  44. English, A.R., Retsema, J.A., Girard, A.E., Lynch, J.E., and Barth, W.E., 1978, CP-45.899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization., Antimicrob. Agents Chemother, 14:414.PubMedCrossRefGoogle Scholar
  45. Fisher, J., Charnas, R.L., and Knowles, J.R., 1978, Kinetic studies on the inactivation of Escherichia coli RTEM beta-lactamase by clavulanic acid, Biochemistry, 17:2180.PubMedCrossRefGoogle Scholar
  46. Frère, J.-M., and Joris, B., 1985, Penicillin-sensitive enzymes in peptidoglycan biosynthesis, CRC Crit. Rev. Microbiol, 11:299.CrossRefGoogle Scholar
  47. Ghuysen, J.-M., Charlier, P., Coyette, J., Duez, C., Fonzé, E., Fraipont, C., Goffin, C., Joris, B., and Nguyen-Distéche, M., 1996, Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and mul-tiprotein complexes, Microb. Drug Resist, 2:163.PubMedCrossRefGoogle Scholar
  48. Ghuysen, J.M., 1991, Serine β-lactamases and penicillin-binding proteins, Annu. Rev. Microbiol, 45:37.PubMedCrossRefGoogle Scholar
  49. Ghuysen, J.M., 1997, Penicillin-binding proteins. Wall peptidoglycan assembly and resistance to penicillin: facts, doubts and hopes, J. Int. Antimicrobial Agents, 8:45.CrossRefGoogle Scholar
  50. Gootz, T.D., Sanders, C.C., and Goering, R.V., 1982, Resistance to cefamandole: derepression of beta-lactamases by cefoxitin and mutation in Enterobacter cloacae, J. Infect. Dis, 146:34.PubMedCrossRefGoogle Scholar
  51. Graham, D.W., Ashton, W.T., Barash, L., Brown, J.E., Brown, R.D., Canning, L.F., Chen, A., Springer, J.P., and Rogers, E.F., 1987, Inhibition of the mammalian β-lactamase renal dipeptidase (dehydropeptidase-I) by (Z)-2-(acylamino)-3-substituted-propenoic acids, J. Med. Chem, 30:1074.PubMedCrossRefGoogle Scholar
  52. Gutmann, L., Kitzis, M.D., Billot-Klein, D., Goldstein, F., Tran Van Nhieu, G., Lu, T., Carlet, J., Collatz, E., and Williamson, R., 1988, Plasmid-mediated β-lactamase (TEM-7) involved in resistance to ceftazidime and aztreonam, Rev. Infect. Dis, 10:860.PubMedCrossRefGoogle Scholar
  53. Harrison, M.P., Haworth, S.J., Moss, S.R., Wilkinson, D.M., and Featherstone, A., 1993, The disposition and metabolic fate of 14C-meropenem in man, Xenobiotica, 23:1311–1323.PubMedCrossRefGoogle Scholar
  54. Henquell, C., Chanal, C., Sirot, D., Labia, R., and Sirot, J., 1995, Molecular characterization of nine different types of mutants among 107 inhibitor-resistant TEM β-lactamases from clinical isolates of Escherichia coli, Antimicrob. Agents Chemother, 39:427.PubMedCrossRefGoogle Scholar
  55. Huang, W., and Palzkill, T., 1997, A natural polymorphism in β-lactamase is a global suppressor, Proc. Natl. Acad. Sci. USA, 94:8801.PubMedCrossRefGoogle Scholar
  56. Huang, W., Petrosino, J., Hirsch, M., Shenkin, P.S., and Palzkill, T., 1996, Amino acid sequence determinants of β-lactamase structure and activity, J. Mol Biol, 258:688.PubMedCrossRefGoogle Scholar
  57. Huletsky, A.; Knox, J. R., and Levesque, R. C., 1993, The role of Ser238 and Lys240 in the hydrolysis of third-generation cephalosporins by SHV-type β-lactamases probed by site-directed mutagenesis and three-dimensional modeling, J. Biol Chem, 268:3690.PubMedGoogle Scholar
  58. Huovinen, P., Huovinen, S., and Jacoby, G.A., 1988, Sequence of PSE-2 beta-lactamase, Antimicrob. Agents Chemother, 32:134.PubMedCrossRefGoogle Scholar
  59. Imtiaz, U., Billings, E., Knox, J.R., Manavathu, E.K., Lerner, S.A., and Mobashery, S., 1993, Inactivation of class A β-lactamases by clavulanic acid: the role of arginine-244 in a proposed nonconcerted sequence of events, J. Am. Chem. Soc, 115:4435.CrossRefGoogle Scholar
  60. Imtiaz, U., Billings, E.M., Knox, J.R., and Mobashery, S., 1994, A structure-based analysis of the inhibition of class A β-lactamases by sulbactam, Biochemistry, 33:5728.PubMedCrossRefGoogle Scholar
  61. Jack, G.W., and Richmond, M.H., 1970, Comparative amino acid contents of purified β-lactamases from enteric bacteria, FEBS Lett, 12:30.PubMedCrossRefGoogle Scholar
  62. Jacobs, M.R., Aronoff, S.C., Johenning, S., and Yamabe, S., 1986, Comparative activities of the β-lactamase inhibitors YTR 830 and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads, J. Antimicrob. Chemother, 18:177.PubMedCrossRefGoogle Scholar
  63. Jaurin, B., and Grundstrom, T., 1981, amp C cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of β-lactamases of the penicillinase type, Proc. Natl. Acad. Sci. USA, 78:4897.PubMedCrossRefGoogle Scholar
  64. Jelsch, C., Mourey, L., Masson, J.M., and Samama, J.P., 1993, Crystal structure of Escherichia coli TEM1 β-lactamase at 1.8 Å resolution, Proteins, 16:364.PubMedCrossRefGoogle Scholar
  65. Kahan, F.M., Kropp, H., Sundelof, J.G., and Birnbaum, J.J., 1983, Thienamycin: development of imipenem-cilas-tatin, Antimicrob. Chemother, 12(Suppl. D):1–35.CrossRefGoogle Scholar
  66. Kahan, J.S., Kahan, F.M., Goegelman, R., Currie, S.A., Jackson, M., Stapley, E.O., Miller, T.W., Miller, A.K., Hendlin, D., Mochales, S., Hernandez, S., Woodruff, H.B., and Birnbaum, J., 1979, Thienamycin, a new β-lactam antibiotic. I. Discovery, taxonomy, isolation, and physical properties, J. Antibiot, 32:1.PubMedCrossRefGoogle Scholar
  67. Kim, H.S., and Campbell, B.J., 1982, β-lactamase activity of renal dipeptidase against N-formimidoyl-thienamy-cin, Biochem. Biophys. Res. Commun, 108:1638.PubMedCrossRefGoogle Scholar
  68. Kirby, W.M.M., 1944, Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci, Science, 99:452.PubMedCrossRefGoogle Scholar
  69. Knothe, H., Shah, P., Krcmery, V., Antal, M., and Mitsuhashi, S., 1983, Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marces-cens, Infection, 11:315.PubMedCrossRefGoogle Scholar
  70. Knox, J. R., 1995, Extended-spectrum and inhibitors-resistant TEM-type β-lactamases: mutations, specificity, and three-dimensional structure, Antimicrob. Agents Chemother, 39:2593.PubMedCrossRefGoogle Scholar
  71. Knox, J.R., Moews, P.C., and Frère, J.M., 1996, Molecular evolution of bacterial β-lactam resistance, Chem. Biol, 3:937.PubMedCrossRefGoogle Scholar
  72. Kropp, H., Sundelof, J.G., Hajdu, R., and Kahan, F. M., 1982, Metabolism of thienamycin and related carbapenem antibiotics by the renal dipeptidase, dehydropeptidase, Antimicrob. Agents Chemother, 22:62.PubMedCrossRefGoogle Scholar
  73. Leigh, D.A., Bradnock, K., and Merriner, J.M., 1981, Augmentin (amoxicillin and clavulanic acid) therapy in complicated infections due to beta-lactamase producing bacteria, J. Antimicrob. Chemother, 7:229.PubMedCrossRefGoogle Scholar
  74. Lemozy, J., Sirot, D., Chanal, C., Huc, C., Labia, R., Dabernat, H., and Sirot, J., 1995, First characterization of inhibitor-resistant TEM (IRT) beta-lactamase in Klebsiella pneumoniae strains, Antimicrob. Agents Chemother, 33:2580.CrossRefGoogle Scholar
  75. Li, X.-Z., Ma, D., Livermore, D.M., and Nikaido, H., 1994, Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: Active efflux as a contributing factor to β-lactam resistance, Antimicrob. Agents Chemother, 38:1742.PubMedCrossRefGoogle Scholar
  76. Lobkovsky, E., Moews, P.C., Liu, H., Zhao, H., Frère, J.M., and J. R. Knox, 1993, Evolution of an enzyme activity: crystallographic structure at 2-Å resolution of cephalosporinase from the ampC gene of Enterobacter cloacae P99 and comparison with a class A penicillinase, Proc. Natl. Acad. Sci. USA, 90:11257.PubMedCrossRefGoogle Scholar
  77. Marshall, M.J., Ross, G.W., Chanter, K.V., and Harris, A.M., 1972, Comparison of the substrate specificities of the β-lactamases from Klebsiella aerogenes 1082E and Enterobacter cloacae P99, Appl Microbiol, 23:765.PubMedGoogle Scholar
  78. Massova, I., and Mobashery, S., 1998, Kinship and diversification of bacterial penicillin-binding proteins and β-lactamases, Antimicrob. Agents Chemother 42:1.PubMedCrossRefGoogle Scholar
  79. Massida, O., Rossolini, G.M., and Satta, G., 1991, The Aeromonas hydrophila cphA gene: Molecular heterogeneity among Class B metallo-β-lactamases, J. Bacteriol, 173:4611.Google Scholar
  80. Matagne, A., Lamotte-Brasseur, J., and Frère, J.M., 1993, Interactions between active-site serine β-lactamases and so-called β-lactamase-stable antibiotics. Kinetic and molecular modelling studies, Eur. J. Biochem, 217:61.PubMedCrossRefGoogle Scholar
  81. Maveyraud, L., Massova, I., Brick, C., Miyashita, K., Samama, J.P., and Mobashery, S., 1996, Crystal-structure of 6α-(hydroxymethyl) penicillanate complexed to the TEM-1 β-lactamase from Escherichia coli: evidence on the mechanism of action of a novel inhibitor designed by a computer-aided process, J. Am. Chem. Soc, 118:7435.CrossRefGoogle Scholar
  82. Maveyraud, L., Mourey, L., Kotra, L.P., Pedelacq, J.D., Guille, V., Mobashery, S., and Samama, J.P., 1998, Structural basis for clinical longetivity of carbapenem antibiotics in the face of challenge by the common class A β-lactamases from the antibiotic-resistant bacteria, J. Am. Chem. Soc, 120:9748.CrossRefGoogle Scholar
  83. Medeiros, A.A., 1997, Evolution and dissemination of β-lactamases accelerated by generation of β-lactam antibiotics, Clin. Inf. Diseases, 24:S19.CrossRefGoogle Scholar
  84. Meyer, K.S., Urban, C., Eagan, J.A., Berger, B.J., and Rahal, J.J., 1993, Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins, Ann. Int. Med, 119:353.PubMedGoogle Scholar
  85. Minami, S., Akama, M., Araki, H., Watanabe, Y., Narita, H., Iyobe, S., and Mitsuhashi, S., 1996, Imipenem and cephem resistant Pseudomonas aeruginosa carrying plasmids coding for class B β-lactamase, J. Antimi-crob. Chemother, 37:433.CrossRefGoogle Scholar
  86. Miyashita, K., Massova, I., and Mobashery, S., 1996, Quantification of the extent of attenuation of the rate of turnover chemistry of the TEM-1 β-lactamase by the α-lR-hydroxyethyl group in substrates, Biooig. Med. Chem. Lett, 6:319.CrossRefGoogle Scholar
  87. Miyashita, K., Massova, I., Taibi, P., and Mobashery, S., 1995, Design, synthesis and evaluation of a potent mechanism-based inhibitor for the TEM β-lactamase with implications for the enzyme mechanism, J. Am. Chem. Soc, 117:11055.CrossRefGoogle Scholar
  88. Moews, P.C., Knox, J.R., Dideberg, O., Charlier, P., and Frère, J.M., 1990, β-lactamase of Bacillus licheniformis 749/C at 2 Å resolution, Proteins Struct., Funct 7:156.CrossRefGoogle Scholar
  89. Neu, U.C., 1983, β-Lactamase stability of cefoxitin in comparison with other β-lactam compounds, Diagn. Microbiol. Infect. Dis, 1:313.PubMedCrossRefGoogle Scholar
  90. Nordmann, P., Mariotte, S., Naas, T., Labia, R., and Nicolas, M.-H., 1993, Biochemical properties of a carbap-enem-hydrolyzing β-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli, Antimicrob. Agents Chemother, 37:939.PubMedCrossRefGoogle Scholar
  91. Payne, D.J., Cramp, R., Winstanley, D.J., and Knowles, D.J.C., 1994, Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important β-lactamases, Antimicrob. Agents Chemother, 38:767.PubMedCrossRefGoogle Scholar
  92. Percival, A., Corkill, J.E., Arya, O.P., Rowlands, J., Alergany, C.D., Rees, E., and Annels, E.H., 1976, Penicilli-nase-producing gonococci in Liverpool, The Lancet, 2:1379.CrossRefGoogle Scholar
  93. Perez-Llarena, F.J., Liras, P., Rodriguez-Garcia, A., and Martin, J.F., 1997, A regulatory gene (ccaR) required for cephamycin and clavulanic acid production in Streptomyces clavuligerus: amplification results in overproduction of both β-lactam compounds., J. Bacteriol, 179:2053.PubMedGoogle Scholar
  94. Perilli, M., Felici, A., Franceschini, N., DeSantis, A., Pagani, L., Luzzaro, F., Oratore, A., Rossolini, G.M., Knox, J.R., and Amicosante, G., 1997, Characterization of a new TEM-derived beta-lactamase produced in a Serratia marcescens strain, Antimicrob. Agents Chemother, 41:2374.PubMedGoogle Scholar
  95. Perine, P.L., Schalla, W., Siegel, M.S., Thornsberry, C., Biddle, J., Wong, K.-H., and Thompson, S.E., 1977, Evidence for two distinct types of penicillinase-producing Neisseria gonorrhoeae, The Lancet, 2:993.CrossRefGoogle Scholar
  96. Petit, A., Gergaud, G., Sirot, D., Courvalin, P., and Sirot, J., 1990, Molecular epidemiology of TEM-3 (CTX-1) beta-lactamase, Antimicrob. Agents Chemother, 34:219.PubMedCrossRefGoogle Scholar
  97. Prinarakis, E.E., Miriagou, V., Tzelepi, E., Gazouli, M., and Tzouvelekis, L.S., 1997, Emergence of an inhibitor-resistant beta-lactamase (SHV-10) derived from an SHV-5 variant, Antimicrob. Agents Chemother, 41:838.PubMedGoogle Scholar
  98. Rasheed, J.K., Jay, C., Metchock, B., Berkowitz, F., Weigel, L., Crellin, J., Steward, C., Hill, B., Medeiros, A.A., and Tenover, F.C., 1997, Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Es-cherichia coli during multiple episodes of bacteremia, Antimicrob. Agents Chemother, 41:647.PubMedGoogle Scholar
  99. Rasmussen, B.A., and Bush, K., 1997, Carbapenem-hydrolyzing β-lactamases, Antimicrob. Agents Chemother, 41:223.PubMedGoogle Scholar
  100. Rasmussen, B.A., Bush, K., Keeney, D., Yang, Y., Hare, R., O’Gara, C., and Medeiros, A.A., 1996, Characterization of IMI-1 β-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae, Antimicrob. Agents Chemother, 40:2080.PubMedGoogle Scholar
  101. Reading, C., and Cole, M., 1977, Clavulanic acid: a beta-lactamase inhibitor from Streptomyces clavuligerus, Antimicrob. Agents Chemother, 11:852.PubMedCrossRefGoogle Scholar
  102. Reading, C., and Farmer, T., 1981, The inhibition of beta-lactamases from Gram-negative bacteria by clavulanic acid, Biochem. J, 199:779.PubMedGoogle Scholar
  103. Richman, D. D., 1995, Protease uninhibited. Nature, 374:494.PubMedCrossRefGoogle Scholar
  104. Richmond, M.H., and Sykes, R.B., 1973, The β-lactamases of gram-negative bacteria and their possible physiological role, Adv. Microb. Physiol, 9:31.PubMedCrossRefGoogle Scholar
  105. Roselle, G.A., Bode, R., Hamilton, B., Bibler, M., Sullivan, R., Douce, R., Staneck, J.L., and Bullock, W.E., 1985, Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid, Antimicrob. Agents Chemother, 27:291.PubMedCrossRefGoogle Scholar
  106. Sirot, D., Recule, C., Chaibi, E.B., Bret, L., Croize, J., Chanal-Claris, C., Labia, R., and Sirot, J., 1997, A complex mutant of TEM-1 beta-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate, Antimicrob. Agents Chemother, 41:1322.PubMedGoogle Scholar
  107. Sirot, D., Sirot, J., Labia, R., Morand, A., Courvalin, P., Darfeuille-Michaud, A., Perroux, R., and Ouzel, R., 1987, Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel β-lactamase, J. Antimicrob. Chemother, 20:323.PubMedCrossRefGoogle Scholar
  108. Sowek, J. A., Singer, S. B., Ohringer, S., Mally, M. F., Dougherty, T. J., Gougoutas, J. Z., and Bush, K., 1991, Substitution of lysine at position 104 or 240 of TEM β-lactamase enhances the effect of serine-164 substitution of hydrolysis or affinity for cephalosporins and the monobactam aztreonam, Biochemistry, 30:3179.PubMedCrossRefGoogle Scholar
  109. Spratt, B.G., Jobanputra, V., and Zimmermann, W., 1977, Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli K-12, Antimicrob. Agents Chemother, 12:406.PubMedCrossRefGoogle Scholar
  110. Strynadka, N.C., Adachi, H., Jensen, S.E., Johns, K., Sielecki, A., Betzel, C., Sutoh, K., and James, M.N., 1992, Molecular structure of the acyl-enzyme intermediate in β-lactam hydrolysis at 1.7 Å resolution, Nature, 359:700.PubMedCrossRefGoogle Scholar
  111. Strynadka, N.C.J., Jensen, S.E., Alzari, P.M., and James, M.N.G., 1996, A potent new mode of β-lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1-BLIP complex, Nature Struct. Biol, 3:290.PubMedCrossRefGoogle Scholar
  112. Sykes, R.B., Bonner, D.R., and Bush, K., Georgopapadakou, N.H., 1982, Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria, Antimicrob. Agents Chemother, 21:85.PubMedCrossRefGoogle Scholar
  113. Sykes, R.B., and Matthew, M., 1976, The β-lactamases of gram-negative bacteria and their role in resistance to β-lactam antibiotics, J. Antimicrob. Chemother, 2:115.PubMedCrossRefGoogle Scholar
  114. Taibi, P., and Mobashery, S., Mechanism of turnover of imipenem by the TEM β-lactamase revisited, J. Am. Chem.Soc, 1995, 117:7600.CrossRefGoogle Scholar
  115. Taibi, P., Massova, I., Vakulenko, S.B., Lerner, S.A., and Mobashery, S., 1996, Evidence for structural elasticity of β-lactamases in the course of catalytic turnover of the novel cephalosporin cefepime, J. Am. Chem. Soc, 118:7441.CrossRefGoogle Scholar
  116. Tarpay, M., 1978, Importance of antimicrobial susceptibility testing of Streptococcus pneumoniae, Antimicrob. Agents Chemother, 14:628.PubMedCrossRefGoogle Scholar
  117. Thornsberry, C., Ogilvie, P., Kahn, J., and Mauriz, Y., 1997, Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996–1997 respiratory season Thornsberry, Clyde; Ogilvie, P., Kahn, J., and Mauriz, Y., Diagn. Microbiol. Infect. Dis, 29:249.Google Scholar
  118. Tipper, D.J., and Strominger, J.L., 1965, Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine, Proc. Natl Acad. Sci. U.S.A, 54:1133.PubMedCrossRefGoogle Scholar
  119. Vakulenko, S., Taibi-Tronche, P., Toth, M., Massova, I., Mobashery, S., and Lerner, S.S., Unpublished results.Google Scholar
  120. Vedel, G., Belaaouaj, A., Gilly, L., Labia, R., Philippon, A., Névot, P., and Paul, G., 1992, Clinical isolates of Escherichia coli producing TRI β-lactamases: novel TEM-enzymes conferring resistance to β-lactamase inhibitors, J. Antimicrob. Chemother, 30:449.PubMedCrossRefGoogle Scholar
  121. Voladri, R.K.R., Tummuru, M.K.R., and Kernodle, D.S., 1996, Structure-function relationships among wild-type variants of Staphylococcus aureus β-lactamase: importance of amino acids 128 and 216, J. Bacteriol, 178:7248.PubMedGoogle Scholar
  122. Wells, J.S., Hunter, J.C., Astle, G.L., Sherwood, J.C., Ricca, C.M., Trejo, W.H., Bonner, D.P., and Sykes, R.B., 1982, Distribution of β-lactam and β-lactone producing bacteria in nature, J. Antibiotics, 35:814.CrossRefGoogle Scholar
  123. Yang, Y., Bhachech, N., and Bush, K., 1995, Biochemical comparison of imipenem, meropenem and biapenem: permeability, binding to penicillin-binding proteins, and stability to hydrolysis by β-lactamases, J. Antimicrob. Chemother, 35:75.PubMedCrossRefGoogle Scholar
  124. Yang, Y., Rasmussen, B.A., and Bush, K., 1992, Biochemical characterization of the metallo-β-lactamase Ccr A from Bacteroides fragilis TAL3636, Antimicrob. Agents Chemother, 36:1155.PubMedCrossRefGoogle Scholar
  125. Yang, Y., Wu, P., and Livermore, D.M., 1990, Biochemical characterization of a β-lactamase that hydrolyzes penems and carbapenems for two Serratia marcescens isolates, Antimicrob. Agents Chemother, 34:755.PubMedCrossRefGoogle Scholar
  126. Zafaralla, G., and Mobashery, S., 1992, Facilitation of the Δ2 → Δ1 pyrroline tautomerization of carbapenem antibiotics by the highly conserved arginine-244 of class A β-lactamases during the course of turnover, J. Am. Chem. Soc, 114:1505.CrossRefGoogle Scholar
  127. Zhou, X.Y., Bordon, F., Sirot, D., Kitzis, M.-D., and Gutmann, L., 1994, Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 β-lactamase conferring resistance to β-lactamase inhibitors, Antimicrob. Agents Chemother, 38:1085.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Karen Bush
    • 1
  • Shahriar Mobashery
    • 2
  1. 1.Drug DiscoveryR. W. Johnson Pharmaceutical Research InstituteRaritanUSA
  2. 2.Department of ChemistryWayne State UniversityDetroitUSA

Personalised recommendations