β-laktamazlar: Genel özellikler, Sınıflandırma ve Tarihçe
Synopsis
ß-laktam antibiyotiklere dirençte en sık görülen mekanizma, bu antibiyotiklerin ß-laktamaz enzimleri ile inaktivasyonudur. Bugüne değin çok sayıda ve farklı işlevleri olan ß-laktamazlar bildirilmiştir. Bu yazıda ß-laktamazların etki mekanizması, tarihçesi ve sınıflandırımları özetlenmiştir.
The most common mechanism of resistance to β-lactam antibiotics is the inactivation of these antibiotics by β-lactamase enzymes. To date, many β-lactamases with different functions have been identified. This article provides a summary of the mechanism of action, history, and classification of β-lactamases.
References
Bradford PA, Castanheira M. Mechanisms of resistance to antibacterial agents in Pfaller MA, Carroll CK (Eds.) Manual of Clinical Microbiology 13th edition, Washington DC. ASM press, 2023:1375-1410.
Mora-Ochomogo M, Lohans CT. β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates. RSC Med. Chem. 2021;12: 1623-1639. https://doi.org/ 10.1039/d1md00200g
Opal SM, Pop-Vicas Aurora. Molecular Mechanisms of antibiotic resistance in bacteria. In: Mandell GL, Bennett JE, Dolin R. and Blaser M. J. (Eds.) Principles and Practice of Infectious Diseases. 9th edition. Philadelphia: Churchill Livingstone; 2020:222- 239.
Bush K, Bradford PA. Epidemiology of β-lactamase-producing pathogens. Clin Microbiol Rev. 2020;33:e00047-19. https://doi.org/10.1128/CMR.00047-19.
Bush K. Past and present perspectives on ß-lactamases. Antimicrob Agents Chemother. 2018;62(10): e01076-18. https//doi.org/10.1128/AAC.01076-18.
Mathew A, Harris AM, Marshall MJ, Ross GW. The use of analytical isoelectric focusing for detection and identification of beta-lactamases. J Gen Microbiol. 1975 ;88(1):169-78. doi: 10.1099/00221287-88-1-169.
Gür D, Akalin HE, Baykal M, Doğrul F. Yeni kuşak beta-laktam antibiyotiklere dirençli Klebsiella ve Enterobacter suşlarinda "Isoelectric Focusing" yöntemi kullanilarak beta-laktamaz enzimlerinin tiplendirilmesi. Mikrobiyol Bul. 1992;26(1):1-11.
Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14(4):933-51, doi: 10.1128/CMR.14.4.933-951.2001.
Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995;39(6):1211-33. doi: 10.1128/AAC.39.6.121
Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother 2010; 54(3):969-76. doi: 10.1128/AAC.01009-09. Epub 2009 Dec 7.
Livermore DM. ß-lactamases in Laboratory and Clinical Resistance. Clin Microbiol Rev 1995; 8:557-584.
Hall BG, Barlow M. Evolution of the serine beta-lactamases: past, present and future. Drug Resist Updat. 2004;7:111–123. https://doi.org/101016/j.drup.2004.02.003.
Barlow M, Hall BG. Phylogenetic analysis shows that the OXA beta-lactamase genes have been on plasmids for millions of years. J Mol Evol. 2002;55:314 –321. https://doi.org/10.1007/s00239-002-2328-y.
Bhullar K, Waglechner N, Pawlowski A, et al. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS One. 2012;7(4):e34953. doi: 10.1371/journal.pone.0034953. Epub 2012 Apr 11.
Bradford PA. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 200114:933–951.
Cetin ET, Ang 0. Staphylococci resistant to methicillin (calbenin). Br Med J. 1962;51:2.
Akman M. Patojen stafilokoklarin antibiyotiklere direnç oranlarindaki artiş 1958-59, 1961-62 ve 1965-66 yillarinda 910 suş ve 5 antibiyotikle yaptiğimiz araştirmalara ait sonuçlarin mukayesesi. Turk Hij Tecr Biyol Derg (1961). 1966;26(3):234-44.
Gur D, Akalin HE, Baykal M. Resistance of gram negative bacteria to new generation cephalosporins and the role of beta-lactamases in this type of resistance. Mikrobiyol Bült 1988; 22:193-8.
Gür D, Pitt TL, Hall LMC, Akalın HE, Livermore DM. Diversity of klebsiellae with extended-spectrum beta-lactamases at a Turkish University Hospital. J Hosp Infect 1992;22:163-166.
Hall LMC, Livermore DM, Gür D, Akova M, Akalın HE. OXA-11, an extended-spectrum variant of OXA-10 (PSE-2) -lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother 1993;37:1637-1644.
Danel F, Hall LMC, Duke B, Gür D, Livermore DM. OXA-17, a further extended-spectrum variant of OXA-10 ß-lactamase, isolated from Pseudomonas aeruginosa. Antimicrob Agents Chemother 1999;43: 1362-1366.
Danel F, Hall LMC, Gür D, Akalın HE, Livermore DM.Transferable production of PER-1 ß-lactamase in Pseudomonas aeruginosa. J Antimicrob Chemother. 1995;35:281-294.
Nordmann P, Ronco E, Naas T, Duport C, Michel-Briand Y, Labia R. characterization of a novel extended-spectrum ß-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother 1993;37:962-969.
Danel F, Hall LMC, Gür D, Akalın HE, Livermore DM.Transferable production of PER-1 ß-lactamase in Pseudomonas aeruginosa. J Antimicrob Chemother 1995;35:281-294.
Castanheira M, Simner PJ, Bradford PA. Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC Antimicrob Resist. 2021;16;3(3):dlab092. doi: 10.1093/jacamr/dlab092.
Poirel L, Héritier C, Tolün V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2004;48(1):15-22. doi: 10.1128/AAC.48.1.15-22.2004.
Bahar G, Mazzariol A, Koncan R et al. Detection of VIM-5 metallo-beta-lactamase in a Pseudomonas aeruginosa clinical isolate from Turkey. J Antimicrob Chemother. 2004;54(1):282-3. doi: 10.1093/jac/dkh321. Epub 2004 Jun 9.
Cicek AC, Duzgun AO, Saral A, Sandalli C. Determination of a novel integron-located variant (blaOXA-320) of Class D β-lactamase in Proteus mirabilis. J Basic Microbiol. 2014;54(10):1030-5. doi: 10.1002/jobm.201300264. Epub 2013 Sep 11.
Mora-Ochomogo M, Lohans CT. β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates. RSC Med. Chem. 2021;12: 1623-1639. https://doi.org/ 10.1039/d1md00200g
Opal SM, Pop-Vicas Aurora. Molecular Mechanisms of antibiotic resistance in bacteria. In: Mandell GL, Bennett JE, Dolin R. and Blaser M. J. (Eds.) Principles and Practice of Infectious Diseases. 9th edition. Philadelphia: Churchill Livingstone; 2020:222- 239.
Bush K, Bradford PA. Epidemiology of β-lactamase-producing pathogens. Clin Microbiol Rev. 2020;33:e00047-19. https://doi.org/10.1128/CMR.00047-19.
Bush K. Past and present perspectives on ß-lactamases. Antimicrob Agents Chemother. 2018;62(10): e01076-18. https//doi.org/10.1128/AAC.01076-18.
Mathew A, Harris AM, Marshall MJ, Ross GW. The use of analytical isoelectric focusing for detection and identification of beta-lactamases. J Gen Microbiol. 1975 ;88(1):169-78. doi: 10.1099/00221287-88-1-169.
Gür D, Akalin HE, Baykal M, Doğrul F. Yeni kuşak beta-laktam antibiyotiklere dirençli Klebsiella ve Enterobacter suşlarinda "Isoelectric Focusing" yöntemi kullanilarak beta-laktamaz enzimlerinin tiplendirilmesi. Mikrobiyol Bul. 1992;26(1):1-11.
Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14(4):933-51, doi: 10.1128/CMR.14.4.933-951.2001.
Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995;39(6):1211-33. doi: 10.1128/AAC.39.6.121
Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother 2010; 54(3):969-76. doi: 10.1128/AAC.01009-09. Epub 2009 Dec 7.
Livermore DM. ß-lactamases in Laboratory and Clinical Resistance. Clin Microbiol Rev 1995; 8:557-584.
Hall BG, Barlow M. Evolution of the serine beta-lactamases: past, present and future. Drug Resist Updat. 2004;7:111–123. https://doi.org/101016/j.drup.2004.02.003.
Barlow M, Hall BG. Phylogenetic analysis shows that the OXA beta-lactamase genes have been on plasmids for millions of years. J Mol Evol. 2002;55:314 –321. https://doi.org/10.1007/s00239-002-2328-y.
Bhullar K, Waglechner N, Pawlowski A, et al. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS One. 2012;7(4):e34953. doi: 10.1371/journal.pone.0034953. Epub 2012 Apr 11.
Bradford PA. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 200114:933–951.
Cetin ET, Ang 0. Staphylococci resistant to methicillin (calbenin). Br Med J. 1962;51:2.
Akman M. Patojen stafilokoklarin antibiyotiklere direnç oranlarindaki artiş 1958-59, 1961-62 ve 1965-66 yillarinda 910 suş ve 5 antibiyotikle yaptiğimiz araştirmalara ait sonuçlarin mukayesesi. Turk Hij Tecr Biyol Derg (1961). 1966;26(3):234-44.
Gur D, Akalin HE, Baykal M. Resistance of gram negative bacteria to new generation cephalosporins and the role of beta-lactamases in this type of resistance. Mikrobiyol Bült 1988; 22:193-8.
Gür D, Pitt TL, Hall LMC, Akalın HE, Livermore DM. Diversity of klebsiellae with extended-spectrum beta-lactamases at a Turkish University Hospital. J Hosp Infect 1992;22:163-166.
Hall LMC, Livermore DM, Gür D, Akova M, Akalın HE. OXA-11, an extended-spectrum variant of OXA-10 (PSE-2) -lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother 1993;37:1637-1644.
Danel F, Hall LMC, Duke B, Gür D, Livermore DM. OXA-17, a further extended-spectrum variant of OXA-10 ß-lactamase, isolated from Pseudomonas aeruginosa. Antimicrob Agents Chemother 1999;43: 1362-1366.
Danel F, Hall LMC, Gür D, Akalın HE, Livermore DM.Transferable production of PER-1 ß-lactamase in Pseudomonas aeruginosa. J Antimicrob Chemother. 1995;35:281-294.
Nordmann P, Ronco E, Naas T, Duport C, Michel-Briand Y, Labia R. characterization of a novel extended-spectrum ß-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother 1993;37:962-969.
Danel F, Hall LMC, Gür D, Akalın HE, Livermore DM.Transferable production of PER-1 ß-lactamase in Pseudomonas aeruginosa. J Antimicrob Chemother 1995;35:281-294.
Castanheira M, Simner PJ, Bradford PA. Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC Antimicrob Resist. 2021;16;3(3):dlab092. doi: 10.1093/jacamr/dlab092.
Poirel L, Héritier C, Tolün V, Nordmann P. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2004;48(1):15-22. doi: 10.1128/AAC.48.1.15-22.2004.
Bahar G, Mazzariol A, Koncan R et al. Detection of VIM-5 metallo-beta-lactamase in a Pseudomonas aeruginosa clinical isolate from Turkey. J Antimicrob Chemother. 2004;54(1):282-3. doi: 10.1093/jac/dkh321. Epub 2004 Jun 9.
Cicek AC, Duzgun AO, Saral A, Sandalli C. Determination of a novel integron-located variant (blaOXA-320) of Class D β-lactamase in Proteus mirabilis. J Basic Microbiol. 2014;54(10):1030-5. doi: 10.1002/jobm.201300264. Epub 2013 Sep 11.
Pages
35-44
Published
April 22, 2026
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