Chapter 6 : β-Lactamases: Historical Perspectives

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β-lactamases are arguably the most well-studied antibiotic resistance determinants that have been described, with over 450 unique enzymes currently identified. Molecular relationships, as well as functional relationships, exist between the β-lactamases and penicillin binding proteins (PBPs), the essential enzymes involved in the terminal stages of bacterial cell wall synthesis. Two sets of β-lactamases classification schemes have evolved, based on either structural or functional descriptions of the enzymes. Fortuitously, the two schemes fit together according to major divisions but show some diversity among various subgroups for each of the divisions as shown. Microbiological methods have traditionally indicated the potential for β-lactamase production, based on susceptibility profiles for β-lactam-containing agents. In multiple surveys conducted during the late 1970s the most commonly identified plasmid-encoded β-lactamases among the were the broad-spectrum (group 2b) SHV-1 and TEM-1 or TEM-2 β-lactamase, followed by the oxacillinhydrolyzing OXA-1 enzyme. In the current age of rapid nucleotide sequencing, molecular and epidemiological characterizations of numerous β-lactamase genes in a wide variety of organisms have been reported. The chapter describes important new enzymes characterized in the published literature since the year 2000. The reported incidence of these β-lactamases depends, in part, on the laboratory technique used for detection by the clinical laboratory, and the type of β-lactamase varies by country and by region. Finally, the search for new β-lactamases in environmental isolates will serve to expand this important family of enzymes that are expected to continue as a major chapter in the story on antibiotic resistance.

Citation: Bush K, Bradford P. 2007. β-Lactamases: Historical Perspectives, p 67-79. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch6

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Outer Membrane Proteins
Antibacterial Agents
Bacterial Cell Wall
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1. Abraham, E. P., and, E. Chain. 1940. An enyzme from bacteria able to destroy penicillin. Nature 146:837.
2. Afazal-Shah, M.,, N. Woodford, and, D. M. Livermore. 2001. Characterization of OXA-25, OXA-26, and OXA-27, molecular class D β-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii. Antimicrob. Agents Chemother. 45:583588.
3. Aibinu, I. E.,, V. C. Ohaegbulam,, E. A. Adenipekun,, F. T. Ogunsola,, T. O. Odugbemi, and, B. J. Mee. 2003. Extended-spectrum β-lactamase enzymes in clinical isolates of Entero-bacter species from Lagos, Nigeria. J. Clin. Microbiol. 41:21972200.
4. Ambler, R. P. 1980. The structure of β-lactamases. Philos. Trans. R. Soc. Lond. B 289:321331.
5. Armand-Lefèvre, L.,, V. Leflon-Guibout,, J. Bredin,, F. Bar-guellil,, A. Amor,, J. M. Pagès, and, M.-H. Nicolas-Chanoine. 2003. Imipenem resistance in Salmonella enterica serovar Wein related to porin loss and CMY-4 β-lactamase production. Antimicrob. Agents Chemother. 47:11651168.
6. Barnes, J. M. 1947. Penicillin and B. anthracis. J. Pathol. Bacteriol. LIX:113125.
7. Bellais, S.,, D. Aubert,, T. Naas, and, P. Nordmann. 2000. Molecular and biochemical heterogeneity of class B carbapenem-hydrolyzing β-lactamases in Chryseobacterium meningosepticum. Antimicrob. Agents Chemother. 44:18781886.
8. Bellais, S.,, D. Girlich,, A. Karim, and, P. Nordmann. 2002. EBR-1, a novel Ambler subclass B1 β-lactamase from Empedobacter brevis. Antimicrob. Agents Chemother. 46:32233227.
9. Bellais, S.,, T. Naas, and, P. Nordmann. 2002. Genetic and biochemical characterization of CGB-1, an Ambler class B carbapenem-hydrolyzing β-lactamase from Chryseo-bacterium gleum. Antimicrob. Agents Chemother. 46:27912796.
10. Bellais, S.,, L. Poirel,, N. Fortineau,, J. W. Decousser, and, P. Nordmann. 2001. Biochemical-genetic characterization of the chromosomally encoded extended-spectrum class A β-lactamase from Rahnella aquatilis. Antimicrob. Agents Chemother. 45:29652968.
11. Benedict, R. G.,, W. H. Schmidt, and, R. D. Coghill. 1945. Penicillin. VII. Penicillinase. Arch. Biochem. 8:377384.
12. Beuchef-Havard, A.,, G. Arlet,, V. Gautier,, R. Labia,, P. Grimont, and, A. Philippon. 2003. Molecular and biochemical characterization of a novel class A β-lactamase (HER-1) from Escherichia hermannii. Antimicrob. Agents Chemother. 47:26692673.
13. Bou, G.,, M. Cartelle,, M. Tomas,, D. Canele,, F. Molina,, R. Moure,, J. M. Eiros, and, A. Guerrero. 2002. Identification and broad dissemination of the CTX-M-14 β-lactamase in different Escherichia coli strains in the Northwest area of Spain. J. Clin. Microbiol. 40:40304036.
14. Bradford, P. A. 2001. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin. Microbiol. Rev. 14:933951.
15. Bradford, P. A.,, S. Bratu,, C. Urban,, M. Visalli,, N. Mariano,, D. L. Landman,, J. J. Rahal,, S. Brooks,, S. Cebular, and, J. Quale. 2004. Emergence of carbapenem-resistant Klebsiella spp. possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 β-lactamases in New York City. Clin. Infect. Dis. 39:5560.
16. Bradford, P. A.,, C. Urban,, N. Mariano,, S. J. Projan,, J. J. Rahal, and, K. Bush. 1997. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC β-lactamase and the loss of an outer membrane protein. Antimicrob. Agents Chemother. 41:563569.
17. Brinas, L.,, M. A. Moreno,, M. Zarazaga,, C. Porerro,, Y. Sáenz,, M. García,, L. Dominguez, and, C. Torres. 2003. Detection of CMY-2, CTX-M-14, and SHV-12 β-lactamases in Escherichia coli fecal-sample isolates from healthy chickens. Antimicrob. Agents Chemother. 47:20562058.
18. Brown, D. F. J., and, P. E. Reynolds. 1980. Intrinsic resistance to beta-lactam antibiotics in Staphylococcus aureus. FEBS Lett. 122:275278.
19. Bush, K. 1997. The evolution of β-lactamases, p. 152166. In D. J. Chadwick and, J. Goode (ed.), Antibiotic Resistance: Origins, Evolution, Selection and Spread, vol. 207. John Wiley & Sons, Chichester, United Kingdom.
20. Bush, K. 2002. The impact of beta-lactamases on the development of novel antimicrobial agents. Curr. Opin. Investig. Drugs 3:12841290.
21. Bush, K. 2003. Structural basis of resistance to β-lactamase inhibitors, abstr. 1790, p. 531. In Program and Abstracts of 43rd ICAAC, 1417 September 2003, Chicago, IL.
22. Bush, K.,, G. A. Jacoby, and, A. A. Medeiros. 1995. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39:12111233.
23. Bush, K., and, R. B. Sykes. 1986. Methodology for the study of β-lactamases. Antimicrob. Agents Chemother. 30:610.
24. Cao, V.,, T. Lambert,, D. Q. Nhu,, H. K. Loan,, N. K. Hoang,, G. Arlet, and, P. Courvalin. 2002. Distribution of extended-spectrum β-lactamases in clinical isolates of Enterobacteriaceae in Vietnam. Antimicrob. Agents Chemother. 46:37393743.
25. Chu, Y.-W.,, M. Afzal-Shah,, E. T. S. Houang,, M.-F. I. Palepou,, D. J. Lyon,, N. Woodford, and, D. M. Livermore. 2001. IMP-4, a novel metallo-β-lactamase from nosocomial Acinetobacter spp. collected in Hong Kong between 1994 and 1998. Antimicrob. Agents Chemother. 45:710714.
26. Corkill, J. E.,, L. E. Cuevas,, R. Q. Gurgel,, J. Greensill, and, C. A. Hart. 2001. SHV-27, a novel cefotaxime-hydrolysing β-lactamase, identified in Klebsiella pneumoniae isolates from a Brazilian hospital. J. Antimicrob. Chemother. 47:463465.
27. Cornaglia, G.,, A. Mazzariol,, L. Lauretti,, G. M. Rossolini, and, R. Fontana. 2000. Hospital outbreak of carbapenem-resistant Pseudomonas aeruginosa producing VIM-1, a novel transferable metallo-β-lactamase. Clin. Infect. Dis. 31:11191125.
28. Dalla-Costa, L. M.,, J. M. Coelho,, H. A. P. H. M. Souza,, M. E. S. Castro,, C. J. N. Stier,, K. L. Bragagnolo,, A. Rea-Neto,, S. R. Penteado-Filho,, D. M. Livermore, and, N. Woodford. 2003. Outbreak of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme in Curitiba, Brazil. J. Clin. Microbiol. 41:34033406.
29. Da Silva, G. J.,, M. Correia,, C. Vital,, G. Ribeiro,, J. C. Sousa,, R. Leitão,, L. Peixe, and, A. Duarte. 2002. Molecular characterization of blaIMP-5, a new integron-borne metallo-β-lactamase gene from an Acinetobacter baumannii nosocomial isolate from Portugal. FEMS Microbiol. Lett. 215:3339.
30. Decousser, J.-W.,, L. Poirel, and, P. Nordmann. 2001. Characterization of a chromosomally encoded extended-spectrum class A β-lactamase from Kluyvera cryocrescens. Antimicrob. Agents Chemother. 45:35953598.
31. Docquier, J.-D.,, F. Pantanella,, F. Giuliani,, M. C. Thaller,, G. Amicosante,, M. Galleni,, J.-M. Frère,, K. Bush, and, G. M. Rossolini. 2002. CAU-1, a subclass B3 metallo-β-lactamase of low substrate affinity encoded by an ortholog present in the Caulobacter crescentus chromosome. Antimicrob. Agents Chemother. 46:18231830.
32. Docquier, J.-D.,, M. L. Riccio,, C. Mugnaioli,, F. Luzzaro,, A. Endimiani,, A. Toniolo,, G. Amicosante, and, G. M. Rossolini. 2003. IMP-12, a new plasmid-encoded metallo-β-lactamase from a Pseudomonas putida clinical isolate. Antimicrob. Agents Chemother. 47:15221528.
33. Doi, Y.,, N. Shibata,, K. Shibayama,, K. Kamachi,, H. Kurkawa,, K. Yokoyama,, T. Yagi, and, Y. Arakawa. 2002. Characterization of a novel plasmid-mediated cephalosporinase (CMY-9) and its genetic environment in an Escherichia coli clinical isolate. Antimicrob. Agents Chemother. 46:24272434.
34. Dowson, C. G.,, A. Hutchison,, J. A. Brannigan,, R. C. George,, D. Hansman,, J. Linares,, A. Tomasz,, J. M. Smith, and, B. G. Spratt. 1989. Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc. Natl. Acad. Sci. USA 86:88428846.
35. Duarte, A.,, F. Boavida,, F. Grosso,, M. Correia,, L. M. Lito,, J. Melo Cristino, and, M. J. Salgado. 2003. Outbreak of GES-1 β-lactamase-producing multidrug-resistant Klebsiella pneumoniae in a university hospital in Lisbon, Portugal. Antimi-crob. Agents Chemother. 47:14811482.
36. Dubois, V.,, L. Poirel,, C. Marie,, C. Arpin,, P. Nordmann, and, C. Quentin. 2002. Molecular characterization of a novel class 1 integron containing blaGES-1 and a fused product of aac(3)-Ib/aac(6p)-I-bp gene cassettes in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 46:638645.
37. Duthie, E. C. 1944. The production of penicillinase by organisms of the subtilis group. Br. J. Exp. Pathol. 25:96100.
38. Duthie, E. S. 1947. The production of stable potent preparations of penicillinase. J. Gen. Microbiol. 1:370377.
39. Essack, S. Y.,, L. M. C. Hall,, D. G. Pillay,, M. L. McFaydyen, and, D. M. Livermore. 2001. Complexity and diversity of Klebsiella pneumoniae strains with extended-spectrum β-lactamases isolated in 1994 and 1996 at a teaching hospital in Durban, South Africa. Antimicrob. Agents Chemother. 45:8895.
40. Fihman, V.,, M. Rottman,, Y. Benzerara,, F. Delisle,, R. Labia,, A. Philippon, and, G. Arlet. 2002. BUT-1: a new member in the chromosomal inducible class C β-lactamases family from a clinical isolate of Buttiauxella sp. FEMS Microbiol. Lett. 213:103111.
41. Fosse, T.,, C. Giraud-Morin,, I. Madinier, and, R. Labia. 2003. Sequence analysis and biochemical characterization of chromosomal CAV-1 (Aeromonas caviae), the parental cephalosporinase of plasmid-mediated AmpC ’FOX’ cluster. FEMS Microbiol. Lett. 222:9398.
42. Foster, J. W. 1945. Acid formation from penicillin during enzymatic inactivation. Science 101:205.
43. Frère, J.-M., and, B. Joris. 1985. Penicillin-sensitive enzymes in peptidoglycan biosynthesis. CRC Crit. Rev. Microbiol. 11:299396.
44. Gales, A. C.,, L. C. Menezes,, S. Silbert, and, H. S. Sader. 2003. Dissemination in distinct Brazilian regions of an epidemic carbapenem-resistant Pseudomonas aeruginosa producing SPM metallo-β-lactamase. J. Antimicrob. Che-mother. 52:699702.
45. Giakkoupi, P.,, G. Petrikkos,, L. S. Tzouvelekis,, S. Tsonas, The WHONET GREECE Study Group, N. J. Legakis, and, A. C. Vatopoulos. 2003. Spread of integron-associated VIM-type metallo-β-lactamase genes among imipenem-nonsusceptible Pseudomonas aeruginosa strains in Greek hospitals. J. Clin. Microbiol. 41:822825.
46. Giakkoupi, P.,, L. S. Tzouvelekis,, A. Tsakris,, V. Loukova,, D. Sofianou, and, E. Tzelepi. 2000. IBC-1, a novel integron-associated class A β-lactamase with extended-spectrum properties produced by an Enterobacter cloacae clinical strain. Antimicrob. Agents Chemother. 44:22472253.
47. Giakkoupi, P.,, A. Xanthaki,, M. Kanelopoulou,, A. Vlahaki,, V. Miragou,, S. Kontou,, E. Papfraggas,, H. Malamou-Lada,, L. S. Tzouvelekis,, N. J. Legakis, and, A. C. Vatopoulos. 2003. VIM-1 metallo-β-lactamase-producing Klebsiella pneumoniae strains in Greek hospitals. J. Clin. Microbiol. 41:38933896.
48. Gibb, A. P.,, C. Tribuddharat,, R. A. Moore,, T. J. Louie,, W. Krulicki,, D. M. Livermore,, M.-F. I. Palepou, and, N. Wood-ford. 2002. Nosocomial outbreak of carbapenem-resistant Pseudomonas aeruginosa with a new blaIMP allele, blaIMP-7. Antimicrob. Agents Chemother. 46:255258.
49. Granier, S. A.,, V. Leflon-Guibout,, F. W. Goldstein, and, M.-H. Nicolas-Chanoine. 2003. New Klebsiella oxytoca β-lactamase genes blaOXY-3 and blaOXY-4 and a third genetic group of K. oxytoca based on blaOXY-3. Antimicrob. Agents Chemother. 47:29222928.
50. Hayes, M. V.,, C. J. Thomson, and, S. G. B. Amyes. 1994. Three beta-lactamases isolated from Aeromonas salmonicida, including a carbapenemase not detectable by conventional methods. Eur. J. Clin. Microbiol. Infect. Dis. 13:805811.
51. Hedges, R. W.,, N. Datta,, P. Kontomichalou, and, J. T. Smith. 1974. Molecular specificities of R factor-determined beta-lactamases: correlation with plasmid compatibility. J. Bacteriol. 117:5662.
52. Henry, R. J., and, R. D. Housewright. 1947. Studies on peni-cillinase. II. Manometric method of assaying penicillinase and penicillin, kinetics of the penicillin-penicillinase reaction, and the effects of inhibitors on penicillinase. J. Biol. Chem. 167:559571.
53. Ho, S. E.,, G. Subramaniam,, S. Palasubramaniam, and, P. Navaratnam. 2002. Carbapenem-resistant Pseudomonas aeruginosa in Malaysia producing IMP-7 β-lactamase. Antimicrob. Agents Chemother. 46:32863287.
54. Hou, J. P., and, J. W. Poole. 1972. Measurement of beta-lactamase activity and rate of inactivation of penicillins by a pH-stat alkalimetric titration method. J. Pharma. Sci. 61:15941598.
55. Humeniuk, G.,, G. Arlet,, R. Labia,, P. Grimont, and, A. Philippon. 2000. Presented at the Reunion Interdisciplinaire de Chimiotherapie Anti-Infectieuse, Paris, France.
56. Huovinen, P.,, S. Huovinen, and, G. A. Jacoby. 1988. Sequence of PSE-2 beta-lactamase. Antimicrob. Agents Chemother. 32:134136.
57. Ito, H.,, Y. Arakawa,, S. Ohsuka,, R. Wacharotayankun,, N. Kato, and, M. Ohta. 1995. Plasmid-mediated dissemination of the metallo-β-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens. Antimicrob. Agents Chemother. 39:824829.
58. Iyobe, S.,, H. Kusadokoro,, A. Takahashi,, S. Yomoda,, T. Okubo,, A. Nakamura, and, K. O’Hara. 2002. Detection of a variant metallo-β-lactamase, IMP-10, from two unrelated strains of Pseudomonas aeruginosa and an Alcaligenes xylosoxidans strain. Antimicrob. Agents Chemother. 46:20142016.
59. Jaurin, B., and, T. Grundstrom. 1981. ampC 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 78:48974901.
60. Jeong, S. H.,, K. Lee,, Y. Chong,, J. H. Yum,, S. H. Lee,, H. J. Choi,, J. M. Kim,, K. H. Park,, B. H. Han,, S. W. Lee, and, T. S. Jeong. 2003. Characterization of a new integron containing VIM-2, a metallo-β-lactamase gene cassette, in a clinical isolate of Enterobacter cloacae. J. Antimicrob. Chemother. 51:397400.
61. Karim, A.,, L. Poirel,, S. Nagarajan, and, P. Nordmann 2001. Plasmid-mediated extended-spectrum β-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol. Lett. 201:237241.
62. Kariuki, S.,, J. E. Corkill,, G. Revathi,, R. Musoke, and, C. A. Hart. 2001. Molecular characterization of a novel plasmid-encoded cefotaximase (CTX-M-12) found in clinical Klebsi-ella pneumoniae isolates from Kenya. Antimicrob. Agents Chemother. 45:21412143.
63. Kartali, G.,, E. Tzelepi,, S. Pournaras,, C. Kontopoulou,, F. Kontos,, D. Sofianou,, A. N. Maniatis, and, A. Tsakris. 2002. Outbreak of infections caused by Enterobacter cloacae producing the integron-associated β-lactamase IBC in a neonatal intensive care unit of a Greek hospital. Antimicrob. Agents Chemother. 46:15771580.
64. Kim, Y.-K.,, H. Pai,, H.-J. Lee,, S.-E. Park,, E.-H. Choi,, J. Kim,, J.-H. Kim, and, E.-C. Kim. 2002. Bloodstream infections by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob. Agents Chemother. 46:14811491.
65. Kirby, W. M. N. 1944. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science 99:452453.
66. Laraki, N.,, M. Galleni,, I. Thamm,, M. L. Riccio,, G. Amico-sante,, J.-M. Frere, and, G. M. Rossolini. 1999. Structure of In31, a blaIMP-containing Pseudomonas aeruginosa integron phyletically related to In5, which carries an unusual array of gene cassettes. Antimicrob. Agents Chemother. 43:890901.
67. Lee, K.,, J. B. Lim,, J. H. Yum,, D. Yong,, Y. Chong,, J. M. Kim, and, D. M. Livermore. 2002. blaVIM-2 cassette-containing novel integrons in metallo-β-lactamase-producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital. Antimi-crob. Agents Chemother. 46:10531058.
68. Liassine, N.,, S. Madec,, B. Ninet,, C. Metral,, M. Fouchereau-Peron,, R. Labia, and, R. Auckenthaler. 2002. Postneurosur-gical meningitis due to Proteus penneri with selection of a ceftriaxone-resistant isolate: analysis of chromosomal class A β-lactamase HugA and its LysR-type regulatory protein HugR. Antimicrob. Agents Chemother. 46:216219.
69. Livermore, D. M. 1998. β-lactamase-mediated resistance and opportunities for its control. J. Antimicrob. Chemother. 41:2543.
70. Lopez-Otsoa, F.,, L. Gallego,, K. J. Towner,, L. Tysall,, N. Woodford, and, D. M. Livermore. 2002. Endemic carbape-nem resistance associated with OXA-40 carbapenemase among Acinetobacter baumannii isolates from a hospital in Northern Spain. J. Clin. Microbiol. 40:47414743.
71. Luzzaro, F.,, E. Mantengoli,, M. Perilli,, G. Lombardi,, V. Orlandi,, A. Orsatti,, G. Amicosante,, G. M. Rossolini, and, A. Toniolo. 2001. Dynamics of a nosocomial outbreak of multidrug-resistant Pseudomonas aeruginosa producing PER-1 extended-spectrum β-lactamase. J. Clin. Microbiol. 39:18651870.
72. Madinier, I.,, T. Fosse,, J. Giudicelli, and, R. Labia. 2001. Cloning and biochemical characterization of a class A β-lactamase from Prevotella intermedia. Antimicrob. Agents Chemother. 45:23862389.
73. Mainardi, J.-L.,, P. Mugnier,, A. Coutrot,, A. Buu-Hoi,, E. Collatz, and, L. Gutmann. 1997. Carbapenem resistance in a clinical isolate of Citrobacter freundii. Antimicrob. Agents Chemother. 41:23522354.
74. Makanera, A.,, G. Arlet,, V. Gautier, and, M. Manai. 2003. Molecular epidemiology and characterization of plasmid-encoded β-lactamases produced by Tunisian clinical isolates of Salmonella enterica serotype Mbandaka resistant to broad-spectrum cephalosporins. J. Clin. Microbiol. 41:29402945.
75. Mammeri, H.,, L. Poirel,, N. Mangeny, and, P. Nordmann. 2003. Chromosomal integration of a cephalosporinase gene from Acinetobacter baumannii into Oligella urethralis as a source of acquired resistance to β-lactams. Antimicrob. Agents Chemother. 47:15361542.
76. Massova, I., and, S. Mobashery. 1998. Kinship and diversification of bacterial penicillin-binding proteins and β-lactamases. Antimicrob. Agents Chemother. 42:117.
77. Matagne, A.,, A. Dubus,, M. Galleni, and, J.-M. Frere. 1999. The beta-lactamase cycle: a tale of selective pressure and bacterial ingenuity. Nat. Prod. Rep. 16:119.
78. Matthew, M., and, A. M. Harris. 1976. Identification of β-lactamases by analytical isoelectric focusing: correlation with bacterial taxonomy. J. Gen. Microbiol. 94:5567.
79. Matthew, M.,, A. M. Harris,, M. J. Marshall, and, G. W. Ross. 1975. The use of isoelectric focusing for detection and identification of beta-lactamases. J. Gen. Microbiol. 88:169178.
80. Medeiros, A. A. 2000. Cooperative evolution of mechanisms of beta-lactam resistance. Clin. Microbiol. Infect. 6 (Suppl. 3):35.
81. Medeiros, A. A. 1997. Evolution and dissemination of β-lactamases accelerated by generations of β-lactam antibiotics. Clin. Infect. Dis. 24:S19S45.
82. Melano, R.,, A. Corso,, A. Petroni,, D. Centrón,, B. Orman,, A. Pereyra,, N. Moreno, and, M. Galas. 2003. Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum β-lactamase in a Klebsiella pneumoniae clinical strain isolated in Argentina. J. Antimicrob. Chemother. 52:3642.
83. Melano, R.,, A. Petroni,, A. Garutti,, H. A. Saka,, L. Mange,, F. Pasterán,, M. Rapoport,, A. Rossi, and, M. Galas. 2002. New carbenicillin-hydrolyzing β-lactamase (CARB-7) from Vibrio cholerae non-O1, non-O139 strains encoded by the VCR region of the V. cholerae genome. Antimicrob. Agents Chemother. 46:21622168.
84. Miragou, V.,, L. S. Tzouvelekis,, S. Rossiter,, E. Tzelepi,, F. J. Angulo, and, J. M. Whichard. 2003. Imipenem resistance in a Salmonella clinical strain due to plasmid-mediated class A carbapenemase KPC-2. Antimicrob. Agents Chemother. 47:12971300.
85. Miró, E.,, F. Navarro,, B. Mirelis,, M. Sabaté,, A. Rivera,, P. Coll, and, G. Prats. 2002. Prevalence of clinical isolates of Escherichia coli producing inhibitor-resistant β-lactamases at a university hospital in Barcelona, Spain, over a 3-year period. Antimicrob. Agents Chemother. 46:39913994.
86. Moland, E. S.,, J. A. Black,, J. Ourada,, M. D. Reisbig,, N. D. Hanson, and, K. S. Thomson. 2002. Occurrence of newer β-lactamases in Klebsiella pneumoniae isolates from 24 U.S. hospitals. Antimicrob. Agents Chemother. 46:38373842.
87. Moland, E. S.,, N. D. Hanson,, V. Herrera,, J. A. Black,, T. J. Lockhart,, A. Hossain,, J. A. Johnson,, R. V. Goering, and, K. S. Thomson. 2003. Plasmid-mediated, carbapenem-hydrolysing β-lactamase, KPC-2 in Klebsiella pneumoniae isolates. J. Antimicrob. Chemother. 51:711714.
88. Morin, A.-S.,, L. Poirel,, F. Mory,, R. Labia, and, P. Nord-mann. 2002. Biochemical-genetic analysis and distribution of DES-1, an Ambler class A extended-spectrum β-lactamase from Desulfovibrio desulfuricans. Antimicrob. Agents Chemother. 46:32153222.
89. Naas, T.,, D. Aubert,, N. Fortineau, and, P. Nordmann. 2002. Cloning and sequencing of the β-lactamase gene and surrounding DNA sequences of Citrobacter braakii, Citro-bacter murliniae, Citrobacter werkmanii, Escherichia fergu-sonii and Enterobacter cancerogenus. FEMS Microbiol. Lett. 215:8187.
90. Naas, T.,, S. Bellais, and, P. Nordmann. 2003. Molecular and biochemical characterization of a carbapenem-hydrolysing β-lactamase from Flavobacterium johnsoniae. J. Antimi-crob. Chemother. 51:267273.
91. Nadjar, D.,, R. Labia,, C. Cerceau,, C. Bizet,, A. Philippon, and, G. Arlet. 2001. Molecular characterization of chromosomal class C β-lactamase and its regulatory gene in Ochro-bactrum anthropi. Antimicrob. Agents Chemother. 5:23242330.
92. National Committee for Clinical Laboratory Standards. 2003. Performance Standards for Antimicrobial Susceptibility Testing. NCCLS Approved Standard M100-S13 (M2). National Committee for Clinical Laboratory Standards, Wayne, Pa.
93. National Committee for Clinical Laboratory Standards. 2003. Performance Standards for Antimicrobial Susceptibility Testing. NCCLS Approved Standard M100-S13 (M7). National Committee for Clinical Laboratory Standards, Wayne, Pa.
94. Newton, G. G. F., and, E. P. Abraham. 1956. Isolation of cephalosporin C, a penicillin-like antibiotic containing D-alpha aminoadipic acid. Biochem. J. 62:651658.
95. Niumsup, P., and, V. Wuthiekanun. 2002. Cloning of the class D β-lactamase gene from Burkholderia pseudomallei and studies on its expression in ceftazidime-susceptible and -resistant strains. J. Antimicrob. Chemother. 50:445455.
96. O’Callaghan, C.,, A. Morris,, S. M. Kirby, and, A. H. Shingler. 1972. Novel method for detection of β-lactamases by using a chromogenic cephalosporin substrate. Antimi-crob. Agents Chemother. 1:283288.
97. Oliver, A.,, J. C. Pérez-Díaz,, T. M. Coque,, F. Baquero, and, R. Cantón. 2000. Presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada.
98. Osano, E.,, Y. Arakawa,, R. Wacharotayankun,, M. Ohta,, T. Horii,, H. Ito,, F. Yosimura, and, N. Kato. 1994. Molecular characterization of an enterobacterial metallo β-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob. Agents Chemother. 38:7178.
99. Page, M. I. 1999. The reactivity of beta-lactams, the mechanism of catalysis and the inhibition of beta-lactamases. Curr. Pharm. Des. 5:895913.
100. Petrella, S.,, D. Clermont,, I. Casin,, V. Jarlier, and, W. Sougakoff. 2001. Novel class A β-lactamase Sed-1 from Citrobacter sedlakii: genetic diversity of β-lactamases within the Citrobacter genus. Antimicrob. Agents Chemother. 45:22872298.
101. Petroni, A.,, A. Corso,, R. Melano,, M. L. Cacace,, A. M. Bru,, A. Rossi, and, M. Galas. 2002. Plasmidic extended-spectrum β-lactamases in Vibrio cholerae O1 El Tor isolates in Argentina. Antimicrob. Agents Chemother. 46:14621486.
102. Poirel, L.,, D. Girlich,, T. Naas, and, P. Nordmann. 2001. OXA-28, an extended-spectrum variant of OXA-10, β-lactamase from Pseudomonas aeruginosa and its plasmid-and integron-located gene. Antimicrob. Agents Chemother. 45:447453.
103. Poirel, L.,, P. Kampfer, and, P. Nordmann. 2002. Chromosome-encoded Ambler class A β-lactamase of Kluyvera georgiana, a probable progenitor of a subgroup of CTX-M extended-spectrum β-lactamases. Antimicrob. Agents Chemother. 46:40384040.
104. Poirel, L.,, T. Lambert,, S. Türkoglü,, E. Ronco,, J.-L. Gail-lard, and, P. Nordmann. 2001. Characterization of class I integrons from Pseudomonas aeruginosa that contain the blaVIM-2 carbapenem-hydrolyzing β-lactamase gene and of two novel aminoglycoside resistance gene cassettes. Antimi-crob. Agents Chemother. 45:456552.
105. Poirel, L.,, O. Menuteau,, N. Agoli,, C. Cattoen, and, P. Nor-dmann. 2003. Outbreak of extended-spectrum β-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a French hospital. J. Clin. Microbiol. 41:35423547.
106. Poirel, L.,, I. L. Thomas,, T. Naas,, A. Karim, and, P. Nord-man. 2000. Biochemical sequence analyses of GES-1, a novel class A extended-spectrum β-lactamase, and the class 1 integron IN52 from Klebsiella pneumoniae. Antimicrob. Agents Chemother. 44:622632.
107. Poirel, L.,, G. F. Weldhagen,, T. Naas,, C. D. Champs,, M. G. Dove, and, P. Nordmann. 2001. GES-2, a class A β-lactamase from Pseudomonas aeruginosa with increased hydrolysis of imipenem. Antimicrob. Agents Chemother. 45:25982603.
108. Pollock, M. R. 1965. Purification and properties of penicillinases from two strains of Bacillus licheniformis: a chemical physicochemical and physiological comparison. Biochem. J. 94:666675.
109. Pournaras, S.,, A. Tsakris,, M. Maniati,, L. S. Tzouvelekis, and, A. N. Maniatis. 2002. Novel variant (blaVIM-4) of the metallo-β-lactamase gene blaVIM-1 in a clinical strain of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 46:40264028.
110. Pragai, Z.,, Z. Koczian, and, E. Nagy. 1998. Characterization of the extended-spectrum β-lactamases and determination of the antibiotic susceptibilities of Klebsiella pneumoniae isolates in Hungary. J. Antimicrob. Chemother. 42:401403.
111. Queenan, A. M.,, B. Foleno,, C. Gownley,, E. Wira, and, K. Bush. 2004. Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates tested by using NCCLS ESBL methodology. J. Clin. Microbiol. 42:269.
112. Queenan, A. M.,, S. Jenkins, and, K. Bush. 2001. Cloning and biochemical characterization of FOX-5, an AmpC-type plasmid-encoded β-lactamase from a New York City Klebsiella pneumoniae isolate. Antimicrob. Agents Chemother. 45:31893194.
113. Quinteros, M.,, M. Radice,, N. Gardella,, M. M. Rodriguez,, N. Costa,, D. Korbenfeld,, E. Couto,, G. Gutkind, and Microbiology Study Group. 2003. Extended-spectrum β-lactamases in Enterobacteriaceae in Buenos Aires, Argentina, public hospitals. Antimicrob. Agents Chemother. 47:28642867.
114. Raskine, L.,, I. Borrel,, G. Barnaud,, S. Boyer,, B. Hanau-Bercot,, J. Gravisse,, R. Labia,, G. Arlet, and, M.-J. Sanson-Le-Pors. 2002. Novel plasmid-encoded class C β-lactamase (MOX-2) in Klebsiella pneumoniae from Greece. Antimi-crob. Agents Chemother. 46:22622265.
115. Ross, G. W.,, K. V. Chanter,, A. M. Harris,, S. M. Kirby,, M. J. Marshall, and, C. H. O’Callaghan. 1973. Comparison of assay techniques for beta-lactamase activity. Anal. Bio-chem. 54:916.
116. Sabath, L. D., and, E. P. Abraham. 1965. Cephalosporinase and penicillinase activity of Bacillus cereus. Antimicrob. Agents Chemother. 1:392397.
117. Sabath, L. D., and, E. P. Abraham. 1966. Zinc as a cofactor for cephalosporinase from Bacillus cereus 569. Biochem. J. 98:11c13c.
118. Sanchez, S.,, M. A. McCrackin Stevenson,, C. R. Hudson,, M. Maier,, T. Buffington,, Q. Dam, and, J. J. Maurer. 2002. Characterization of multidrug-resistant Escherichia coli isolates associated with nosocomial infections in dogs. J. Clin. Microbiol. 40:35863595.
119. Schwaber, M. J.,, P. M. Raney,, J. K. Rasheed,, J. W. Biddle,, P. Williams,, J. E. McGowan, Jr., and, F. C. Tenover. 2004. Utility of NCCLS guidelines for identifying extended-spectrum beta-lactamases in non-Escherichia coli and non-Klebsiella spp. of Enterobacteriaceae. J. Clin. Microbiol. 42:294.
120. Shannon, K.,, A. King, and, I. Phillips. 1986. β-Lactamases with high activity against imipenem and Sch 34343 from Aeromonas hydrophila. J. Antimicrob. Chemother. 17:4550.
121. Simm, A. M.,, C. S. Higgins,, S. T. Pullan,, M. B. Avison,, P. Niumsup,, O. Erdozain,, P. M. Bennett, and, T. R. Walsh. 2001. A novel metallo-β-lactamase, Mb11b, produced by the environmental bacterium Caulobacter crescentus. FEBS Lett. 509:350354.
122. Spanu, T.,, F. Luzzaro,, M. Perilli,, G. Amicosante,, A. Toni-olo,, G. Fadda, andThe Italian ESBL Study Group. 2002. Occurrence of extended-spectrum β-lactamases in members of the family Enterobacteriaceae in Italy: implications for resistance to β-lactams and other antimicrobial drugs. Antimicrob. Agents Chemother. 46:196202.
123. Strydnadka, N. C. J.,, H. Adachi,, S. E. Jensen,, K. Johns,, A. Sielecke,, C. Betzel,, K. Sutoh, and, M. N. G. James. 1992. Molecular structure of the acyl-enzyme intermediate in β-lactam hydrolysis at 1.7 A resolution. Nature 359:700705.
124. Sykes, R. B.,, D. P. Bonner,, K. Bush, and, N. H. Georgopa-padakou. 1982. Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob. Agents Chemother. 21:8592.
125. Tenover, F. C.,, P. M. Raney,, P. P. Williams,, J. K. Rasheed,, J. W. Biddle,, A. Oliver,, S. K. Fridkin,, L. Jevitt, and, J. E. McGowan, Jr. 2003. Evaluation of the NCCLS extended-spectrum β-lactamase confirmation methods for Escherichia coli with isolates collected during project ICARE. J. Clin. Microbiol. 41:31423146.
126. Toleman, M. A.,, D. Biedenbach,, D. Bennett,, R. N. Jones, and, T. R. Walsh. 2003. Genetic characterization of a novel metallo-β-lactamase gene blaIMP-13, harboured by a novel Tn5051-type transposon disseminating carbapenemase genes in Europe: report from the SENTRY worldwide antimicrobial surveillance programme. J. Antimicrob. Chemother. 52:583590.
127. Toleman, M. A.,, K. Rolston,, R. N. Jones, and, T. R. Walsh. 2003. Molecular and biochemical characterization of OXA-45, an extended-spectrum class 2dp β-lactamase in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 47:28592863.
128. Vessillier, S.,, J.-D. Docquier,, S. Rival,, J.-M. Frere,, M. Gal-leni,, G. Amicosante,, G. M. Rossolini, and, N. Franceschini. 2002. Overproduction and biochemical characterization of the Chryseobacterium meningosepticum BlaB metallo-β-lactamase. Antimicrob. Agents Chemother. 46:19211927.
129. Vourli, S.,, L. S. Tzouvelekis,, E. Tzelepi,, E. Lebessi,, N. J. Legakis, and, V. Miragou. 2003. Characterization of In111, a class 1 integron that carries the extended-spectrum β-lactamase gene blaIBC-1. FEMS Microbiol. Lett. 225:149153.
130. Walsh, T. R.,, M. A. Toleman,, W. Hryniewicz,, P. M. Bennett, and, R. N. Jones. 2002. Evolution of an integron carrying blaVIM-2 in Eastern Europe: report from the SENTRY antimicrobial surveillance program. J. Antimicrob. Chem-other. 52:116119.
131. Wang, H.,, S. Kelkar,, W. Wu,, M. Chen, and, J. P. Quinn. 2003. Clinical isolates of Enterobacteriaceae producing extended-spectrum β-lactamases: prevalence of CTX-M-3 at a hospital in China. Antimicrob. Agents Chemother. 47:790793.
132. Wang, Z.,, W. Fast, and, S. J. Benkovic. 1999. On the mechanism of the metallo-beta-lactamase from Bacteroides fragilis. Biochemistry 38:1001310023.
133. Winokur, P. L.,, A. Brueggemann,, D. L. DeSalvo,, L. Hoffmann,, M. D. Apley,, E. K. Uhlenhopp,, M. A. Pfaller, and, G. V. Doern. 2000. Animal and human multidrug-resistant, cephalosporin-resistant salmonella isolates expressing a plasmid-mediated CMY-2 AmpC beta-lactamase. Antimi-crob. Agents Chemother. 44:27772783.
134. Winokur, P. L.,, D. L. Vonstein,, L. J. Hoffman,, E. K. Uhlenhopp, and, G. V. Doern. 2001. Evidence for transfer of CMY-2 AmpC beta-lactamase plasmids between Escherichia coli and Salmonella isolates from food animals and humans. Antimicrob. Agents Chemother. 45:27162722.
135. Yamasaki, K.,, M. Komatsu,, T. Yamashita,, K. Shimakawa,, T. Ura,, H. Nishio,, K. Satoh,, R. Washidu,, S. Kinoshita, and, M. Aihara. 2003. Production of CTX-M-3 extended-spectrum β-lactamase and IMP-1 metallo β-lactamase by five Gram-negative bacilli: survey of clinical isolates from seven laboratories collected in 1998 and 2000, in the Kinki region of Japan. J. Antimicrob. Chemother. 51:631638.
136. Yan, J.-J.,, P.-R. Hsueh,, W.-C. Ko,, K.-T. Luh,, S.-H. Tsai,, H.-M. Wu, and, J.-J. Wu. 2001. Metallo-β-lactamases in clinical Pseudomonas isolates in Taiwan and identification of VIM-3, a novel variant of the VIM-2 enzyme. Antimi-crob. Agents Chemother. 45:22242228.
137. Yano, H.,, A. Kuga,, R. Okamoto,, H. Kitasato,, T. Koba-yashi, and, M. Inoue. 2001. Plasmid-encoded metallo-β-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem. Antimicrob. Agents Chemother. 45:13431348.
138. Yigit, H.,, G. J. Anderson,, J. W. Biddle,, C. D. Steward,, J. K. Rasheed,, L. L. Valera,, J. E. McGowan, Jr., and, F. C. Tenover. 2002. Carbapenem resistance in a clinical isolate of Enterobacter aerogenes is associated with decreased expression of OmpF and OmpC porin analogs. Antimicrob. Agents Chemother. 46:38173822.
139. Yigit, H.,, A. M. Queenan,, G. J. Anderson,, A. Domenech-Sanchez,, J. W. Biddle,, C. D. Steward,, S. Alberti,, K. Bush, and, F. C. Tenover. 2001. Novel carbapenem-hydrolyzing β-lactamase, KPC-1 from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45:11511161.
140. Yomoda, S.,, T. Okubo,, A. Takahashi,, M. Murakami, and, S. Iyobe. 2003. Presence of Pseudomonas putida strains harboring plasmids bearing the metallo-β-lactamase gene blaIMP in a hospital in Japan. J. Clin. Microbiol. 41:42464251.
141. Yong, D.,, J. H. Shin,, S. Kim,, Y. Lim,, J. H. Yum,, K. Lee,, Y. Chong, and, A. Bauernfeind. 2003. High prevalence of PER-1 extended-spectrum β-lactamase-producing Acineto-bacter spp. in Korea. Antimicrob. Agents Chemother. 47:17491751.
142. Zhao, S.,, D. G. White,, P. F. McDermott,, S. Friedman,, L. English,, S. Ayers,, J. Meng,, J. J. Maurer,, R. Holland, and, R. D. Walker. 2001. Identification and expression of cephamycinase blaCMY genes in Escherichia coli and Salmonella isolates from food animals and ground meat. Antimi-crob. Agents Chemother. 45:36473650.


Generic image for table
Table 6.1

Summary of β-lactamase classification schemes

Citation: Bush K, Bradford P. 2007. β-Lactamases: Historical Perspectives, p 67-79. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch6
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Table 6.2

Chromosomally encoded β-lactamase genes discovered since 2000

Citation: Bush K, Bradford P. 2007. β-Lactamases: Historical Perspectives, p 67-79. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch6
Generic image for table
Table 6.3

Diversity of plasmid-mediated β-lactamases in various regions of the world

Citation: Bush K, Bradford P. 2007. β-Lactamases: Historical Perspectives, p 67-79. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch6

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