Biochemical Characterization of SHV-55, an Extended-Spectrum Class A β-Lactamase from Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy
2008.0

Abstract

We biochemically characterized the Klebsiella pneumoniae extended-spectrum SHV-55 enzyme carrying the amino acid substitutions Tyr73Phe (as in SHV-28) and Gly2383Ser and Glu2403Lys (both found in SHV-5) identified in a previous study (5). The blaSHV-55 gene was obtained as described by Mendonc¸a et al. (6), and transformants were selected on Luria broth agar supplemented with 30 g of kanamycin/ml and 16 g of amoxicillin/ml. SHV-55 was extracted and purified according to the previously described protocol (6). The Michaelis constant (Km) and catalytic activity (kcat) of purified extracts of SHV-55 were obtained by using a computerized microacidimetric method and a 702 SM Titrino pH-stat apparatus (Metrohm, Herisau, Switzerland) (3). These kinetic parameters were determined and compared to those of the SHV-1 enzyme for 10 --lactams (Table 1). SHV-55 has a high affinity (Km, 5 to 10 M) for penicillins, similar to that of SHV-5 (1) and higher than that of SHV-1 (Km, 11 to 31 M). SHV-55 presented higher affinity values (Km, 9 to 58 M) than SHV-1 (Km, 40 to 257 M) for narrow-, extended-, and broad-spectrum cephalosporins and monobactams. The enzymatic activities (kcats) of SHV-55 for penicillin G and amoxicillin were 84- and 45-fold lower, respectively, than those of SHV-1, and the catalytic efficiency (kcat/Km ratio) against penicillins was more than 10-fold higher for SHV-1 (kcat/Km ratio, 20 to 84 M1 s 1 ) than for SHV-55 (kcat/Km ratio, 2 to 5 M1 s 1 ). However, the enzyme activity and catalytic efficiency against extended- and broad-spectrum cephalosporins were higher for SHV-55 (kcat, 7 to 24 s1 , and kcat/Km ratio, 0.2 to 1 M1 s 1 ) than for SHV-1 (note, however, that the values for monobactam were undeterminable), although the catalytic efficiencies of the two enzymes against cephalothin were similar (kcat/Km ratios, 3.2 and 4.4 M1 s 1 ). Fifty percent inhibitory concentrations (IC50s) indicated that SHV-55 was ninefold more susceptible to the inhibitor activity of clavulanate than SHV-1 (IC50s of clavulanate, 0.02 versus 0.17 M). In conclusion, these results confirmed the extended-spectrum activity of the SHV-55 enzyme, which is important due to the magnitude of extended- and broad-spectrum SHV --lactamases described to date and not biochemically characterized, in spite of the ease of sequencing genes (http://www.lahey.org /studies).

Knowledge Graph

Similar Paper

Biochemical Characterization of SHV-55, an Extended-Spectrum Class A β-Lactamase from Klebsiella pneumoniae
Antimicrobial Agents and Chemotherapy 2008.0
Biochemical Study of a New Inhibitor-Resistant β-Lactamase, SHV-84, Produced by a Clinical Escherichia coli Strain
Antimicrobial Agents and Chemotherapy 2010.0
Molecular and Biochemical Characterization of SHV-56, a Novel Inhibitor-Resistant β-Lactamase fromKlebsiella pneumoniae
Antimicrobial Agents and Chemotherapy 2008.0
The Lys234Arg Substitution in the Enzyme SHV-72 Is a Determinant for Resistance to Clavulanic Acid Inhibition
Antimicrobial Agents and Chemotherapy 2008.0
Homology modeling and docking study of recent SHV type β-lactamses with traditional and novel inhibitors: an in silico approach to combat problem of multiple drug resistance in various infections
Medicinal Chemistry Research 2012.0
Phenotypic and Enzymatic Comparative Analysis of the Novel KPC Variant KPC-5 and Its Evolutionary Variants, KPC-2 and KPC-4
Antimicrobial Agents and Chemotherapy 2009.0
Design and Exploration of Novel Boronic Acid Inhibitors Reveals Important Interactions with a Clavulanic Acid-Resistant Sulfhydryl-Variable (SHV) β-Lactamase
Journal of Medicinal Chemistry 2013.0
Pyrosequencing Using the Single-Nucleotide Polymorphism Protocol for Rapid Determination of TEM- and SHV-Type Extended-Spectrum β-Lactamases in Clinical Isolates and Identification of the Novel β-Lactamase Genes bla <sub>SHV-48</sub> , bla <sub>SHV-105</sub> , and bla <sub>TEM-155</sub>
Antimicrobial Agents and Chemotherapy 2009.0
E240V Substitution Increases Catalytic Efficiency toward Ceftazidime in a New Natural TEM-Type Extended-Spectrum β-Lactamase, TEM-149, from Enterobacter aerogenes and Serratia marcescens Clinical Isolates
Antimicrobial Agents and Chemotherapy 2008.0
Kinetic Characterization of VIM-7, a Divergent Member of the VIM Metallo-β-Lactamase Family
Antimicrobial Agents and Chemotherapy 2008.0