D Sınıfı β-laktamazlar
Özet
D sınıfı β-laktamazlar, Ambler moleküler sınıflamasına göre, A ve C sınıf β-laktamazlar gibi serin hidrolazlar grubundadır. Evrimsel olarak ilişkili olmakla birlikte A ve C β-laktamazlar ile %20’den az homoloji gösterirler. Çoğu, tazobaktam, klavulanik asit, sulbaktam gibi klasik inhibitörlerden etkilenmezler. Avibaktam ve vaborbaktam gibi yeni inhibitörler, bu enzimler üzerinde etkili olabilir. Klinik önemi olan D sınıfı enzimler, özellikle gram negatif bakterilerdeki OXA tipi β-laktamazlar, çoğunlukla plazmidler tarafından kodlanır. OXA β-laktamazlar etki spektrumlarına göre üç alt grupta incelenir: 1. Dar spektrumlu OXA enzimler: Oksasilin ve kloksasilini hidrolize ederler ve klasik inhibitörlerden etkilenmezler. 2. Geniş spektrumlu OXA enzimler: Üçüncü kuşak sefalosporinleri hidrolize edebilirler 3. Karbapenem-hidrolize eden OXA enzimler: Klinik açıdan önemlidirler (örn., A. baumannii’de OXA-23, K. pneumoniae’da OXA-48. OXA enzimlerin laboratuvar tanısında ticari immünokromatografik testler ve MALDI-TOF MS kullanılabilir. PCR bazlı metodlar, RT-qPCR, izotermal PCR ve mikroarrayler, özgül tanıda altın standarttır.
Class D β-lactamases, according to the Ambler molecular classification, are serine hydrolases like class A and C enzymes. Although evolutionarily related, they share less than 20% homology with classes A and C. Most class D β-lactamases are not inhibited by classical inhibitors like tazobactam, clavulanic acid, or sulbactam, but newer inhibitors such as avibactam and vaborbactam can be effective. Clinically important class D enzymes, especially OXA-type β-lactamases in gram negative bacteria, are mainly plasmid-encoded. OXA group β-Lactamases can be divided into three subgroups according to their action spectrum; 1. Narrow-spectrum OXA enzymes: they hydrolyze oxacillin and cloxacillin and are not inhibited by classical inhibitors, 2. Extended-spectrum OXA enzymes: they can hydrolyze third-generation cephalosporins, 3. Carbapenem-hydrolyzing OXA enzymes: they are clinically significant (e.g., OXA-23 in A. baumannii, OXA-48 in K. pneumoniae). Commercial immunochromatographic tests and MALDI-TOF MS can detect OXA enzymes. PCR-based methods, RT-qPCR, isothermal PCR, and microarrays remain the gold standard for specific detection.
Referanslar
K Bush, GA Jacoby, AA Medeiros. A Functional Classification Scheme for β-Lactamases and Its Correlation with Molecular Structure. Antimicrob Agents Chemother. 1995; 39:1211-33.
BA Evans, SG Amyes. OXA β-lactamases. Clin Microbiol Rev. 2014; 27: 241-63.
E-J Yoon, SH Jeong. Class D β-Lactamases. J Antimicrob Chemother 2021; 76: 836-64.
F Khan, B Chaudhary, AU Khan. Class D Type β-Lactamases. In: β-Lactam Reistance in Gram-Negative Bacteria. Eds.:M Shahid, A Singh, H Sami. 2022, Pg.: 125-140. Springer Nature Singapore Pte Ltd.
K Bush, GA Jacoby. Updated functional classification of β-lactamases. Antimicrob Agents Chemother. 2009; 54: 969-76.
K Bush. Past and Present Perspectives on β-Lactamases. Antimicrob Agents Chemother. 2018; 62(10):e01076-18. doi: 10.1128/AAC.01076-18.
M Castanheira, PJ Simner, PA Bradford. Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC-Antimicrobial Resistance. 2021;Issue 3. https://doi.org/10.1093/jacamr/dlab092
T Naas, S Queslati, RA Bonnin, ML Dabos, et al. Β-Lactamase DataBase (BLDB) – Structure and Function. J Enzyme Inhib Med Chem. 2017; 32: 917-19.
Y He, J Lei, X Pan, et al. The hydrolytic water molecule of Class A β-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis. Sci Rep. 2020;10(1):10205 https://doi.org/10.1038/s41598-020-66431-w
NT Antunes, JF Fisher. Acquired Class D β-Lactamases. Antibiotics. 2014;21;3(3):398-434. doi: 10.3390/antibiotics3030398
J Li, Y Li, X Cao, J Zheng, et al. Genome-wide identification and oxacillinase OXA distribution characteristics of Acinetobacter spp. based on a global database. Front Microbiol. 2023;1:14:1174200. doi: 10.3389/fmicb.2023.1174200.
LM Hall, DM Livermore, D Gur, M Akova, HE Akalin. OXA-11, an extended-spectrum variant of OXA-10 (PSE-2) β-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1993;37:1637-44. https://doi.org/10.1128/aac.37.8.1637
F Danel, LCM Hall, D Gür, DM Livermore. OXA-15, an extended-spectrum variant of OXA-2 ß-lactamase, isolated from a Pseudomonas aeruginosa strain. Antimicrob Agents Chemother 1997; 41: 785-790.
F Danel, LMC Hall, D Gür, DM Livermore. OXA-16, a further extended-spectrum variant of OXA-10 ß-lactamase, from two Pseudomonas aeruginosa isolates. Antimicrob Agents Chemother 1998; 42: 3117-3122.
W Scaife, HK Young, RH Paton, GB Amyes. Transferable imipenem-resistance in Acinetobacter species from a clinical source. J Antimicrob Chemother. 1995;36:585–7. 10.1093/jac/36.3.585
L Poirel, C Héritier, V Tolün, P Nordmann. 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
JDD Pitout, G Peirano, MM Kock, KA Strydom, Y Matsumuraf. The Global Ascendency of OXA-48-Type Carbapenemases. Clinical Microbiology Reviews. 2020;33:e00102-19. https://doi .org/10.1128/CMR.00102-19.
L Poirel, M Castanheira, A Carrër, CP Rodriguez, et al. OXA-163, an OXA-48-related class D β-lactamase with extended activity toward expanded-spectrum cephalosporins. Antimicrob Agents Chemother. 2011;55(6):2546-51. doi: 10.1128/AAC.00022-11.
K Bush, PA Bradford. Epidemiology of β-lactamase producing pathogens. Clinical Microbiology Reviews. 2020;33 (2):10.1128/cmr. 00047-19
L Poirel, C Heritier, P Nordmann. Chromosome-encoded ambler class D β-lactamase of Shewanella oneidensis as a progenitor of carbapenem-hydrolyzing oxacillinase. Antimicrob Agents Chemother. 2004; 48:348 –351. https://doi.org/10.1128/AAC.48.1.348-351.2004.
J Schwanbeck, W Bohne, U Hasdemir, U Groß, et al. Detection of a New Resistance-Mediating Plasmid Chimera in a blaOXA-48-Positive Klebsiella pneumoniae Strain at a German University Hospital. Microorganisms.2021;9:720. https://doi.org/10.3390/microorganisms9040720
W Li, S Sun, Q Yang, et al. Comparative Genomic Analysis of Plasmids Harboring blaOXA-48-like Genes in Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology. 2022;12:889654.
SJ Nigro, RM Hall. Structure and context of blaOXA-23 in Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy. 2016;60(6):3753–3757.
European Committee on Antimicrobial Testing (EUCAST), https://www.eucast.org/
Clinical and Laboratory Standards Institute (CLSI)CLSI https://clsi.org/
PJ Simner, JDD Pitout, TC Dingle. Laboratory detection of carbapenemases among Gram-negative organisms. Clin Microbiol Rev. 2024. 37:e00054-22.https://doi.org/10.1128/cmr.00054-22
M Oviaño, MJ Barba, B Fernández, A Ortega, et al. Rapid Detection of OXA-48-Producing Enterobacteriaceae by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. J Clin Microbiol. 2016; 54 754-9. doi: 10.1128/JCM.02496-15.
V Studentova V, L Dadovska, J Hrabak. Direct identification of OXA-48-type carbapenemases by detection of β-lactone-specific signal using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Int J Antimicrob Agents. 2024; 63(5):107130. doi: 10.1016/j.ijantimicag.2024.107130.
Referanslar
K Bush, GA Jacoby, AA Medeiros. A Functional Classification Scheme for β-Lactamases and Its Correlation with Molecular Structure. Antimicrob Agents Chemother. 1995; 39:1211-33.
BA Evans, SG Amyes. OXA β-lactamases. Clin Microbiol Rev. 2014; 27: 241-63.
E-J Yoon, SH Jeong. Class D β-Lactamases. J Antimicrob Chemother 2021; 76: 836-64.
F Khan, B Chaudhary, AU Khan. Class D Type β-Lactamases. In: β-Lactam Reistance in Gram-Negative Bacteria. Eds.:M Shahid, A Singh, H Sami. 2022, Pg.: 125-140. Springer Nature Singapore Pte Ltd.
K Bush, GA Jacoby. Updated functional classification of β-lactamases. Antimicrob Agents Chemother. 2009; 54: 969-76.
K Bush. Past and Present Perspectives on β-Lactamases. Antimicrob Agents Chemother. 2018; 62(10):e01076-18. doi: 10.1128/AAC.01076-18.
M Castanheira, PJ Simner, PA Bradford. Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC-Antimicrobial Resistance. 2021;Issue 3. https://doi.org/10.1093/jacamr/dlab092
T Naas, S Queslati, RA Bonnin, ML Dabos, et al. Β-Lactamase DataBase (BLDB) – Structure and Function. J Enzyme Inhib Med Chem. 2017; 32: 917-19.
Y He, J Lei, X Pan, et al. The hydrolytic water molecule of Class A β-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis. Sci Rep. 2020;10(1):10205 https://doi.org/10.1038/s41598-020-66431-w
NT Antunes, JF Fisher. Acquired Class D β-Lactamases. Antibiotics. 2014;21;3(3):398-434. doi: 10.3390/antibiotics3030398
J Li, Y Li, X Cao, J Zheng, et al. Genome-wide identification and oxacillinase OXA distribution characteristics of Acinetobacter spp. based on a global database. Front Microbiol. 2023;1:14:1174200. doi: 10.3389/fmicb.2023.1174200.
LM Hall, DM Livermore, D Gur, M Akova, HE Akalin. OXA-11, an extended-spectrum variant of OXA-10 (PSE-2) β-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1993;37:1637-44. https://doi.org/10.1128/aac.37.8.1637
F Danel, LCM Hall, D Gür, DM Livermore. OXA-15, an extended-spectrum variant of OXA-2 ß-lactamase, isolated from a Pseudomonas aeruginosa strain. Antimicrob Agents Chemother 1997; 41: 785-790.
F Danel, LMC Hall, D Gür, DM Livermore. OXA-16, a further extended-spectrum variant of OXA-10 ß-lactamase, from two Pseudomonas aeruginosa isolates. Antimicrob Agents Chemother 1998; 42: 3117-3122.
W Scaife, HK Young, RH Paton, GB Amyes. Transferable imipenem-resistance in Acinetobacter species from a clinical source. J Antimicrob Chemother. 1995;36:585–7. 10.1093/jac/36.3.585
L Poirel, C Héritier, V Tolün, P Nordmann. 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
JDD Pitout, G Peirano, MM Kock, KA Strydom, Y Matsumuraf. The Global Ascendency of OXA-48-Type Carbapenemases. Clinical Microbiology Reviews. 2020;33:e00102-19. https://doi .org/10.1128/CMR.00102-19.
L Poirel, M Castanheira, A Carrër, CP Rodriguez, et al. OXA-163, an OXA-48-related class D β-lactamase with extended activity toward expanded-spectrum cephalosporins. Antimicrob Agents Chemother. 2011;55(6):2546-51. doi: 10.1128/AAC.00022-11.
K Bush, PA Bradford. Epidemiology of β-lactamase producing pathogens. Clinical Microbiology Reviews. 2020;33 (2):10.1128/cmr. 00047-19
L Poirel, C Heritier, P Nordmann. Chromosome-encoded ambler class D β-lactamase of Shewanella oneidensis as a progenitor of carbapenem-hydrolyzing oxacillinase. Antimicrob Agents Chemother. 2004; 48:348 –351. https://doi.org/10.1128/AAC.48.1.348-351.2004.
J Schwanbeck, W Bohne, U Hasdemir, U Groß, et al. Detection of a New Resistance-Mediating Plasmid Chimera in a blaOXA-48-Positive Klebsiella pneumoniae Strain at a German University Hospital. Microorganisms.2021;9:720. https://doi.org/10.3390/microorganisms9040720
W Li, S Sun, Q Yang, et al. Comparative Genomic Analysis of Plasmids Harboring blaOXA-48-like Genes in Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology. 2022;12:889654.
SJ Nigro, RM Hall. Structure and context of blaOXA-23 in Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy. 2016;60(6):3753–3757.
European Committee on Antimicrobial Testing (EUCAST), https://www.eucast.org/
Clinical and Laboratory Standards Institute (CLSI)CLSI https://clsi.org/
PJ Simner, JDD Pitout, TC Dingle. Laboratory detection of carbapenemases among Gram-negative organisms. Clin Microbiol Rev. 2024. 37:e00054-22.https://doi.org/10.1128/cmr.00054-22
M Oviaño, MJ Barba, B Fernández, A Ortega, et al. Rapid Detection of OXA-48-Producing Enterobacteriaceae by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. J Clin Microbiol. 2016; 54 754-9. doi: 10.1128/JCM.02496-15.
V Studentova V, L Dadovska, J Hrabak. Direct identification of OXA-48-type carbapenemases by detection of β-lactone-specific signal using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Int J Antimicrob Agents. 2024; 63(5):107130. doi: 10.1016/j.ijantimicag.2024.107130.
