OXA-14, another extended-spectrum variant of OXA-10 (PSE-2) beta-lactamase from Pseudomonas aeruginosa

Danel, Franck; Hall, Lucinda M. C.; Gür, Deniz; Livermore, David M.

doi:10.1128/aac.39.8.1881

Cited by 105 publications

(122 citation statements)

References 11 publications

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“…10,11 OXA-1-like enzymes are sometimes harbored alongside the CTX-M group in K. pneumoniae and E. coli, 10 whereas the OXA-10 derivatives (OXA-11, -14, -16, -17 and -19) exhibiting ESBL activity, and carbapenem-hydrolyzing class D β-lactamases (CHDLs, e.g., OXA-23, -24/40, -48, -51 and -58), are commonly found in Pseudomonas aeruginosa and Acinetobacter baumannii, respectively. [11][12][13] Notably, carbapenemases, especially metallo-β-lactamases, present a far greater risk of treatment failure with the currently available drugs in clinical practice. However, by and large, the prevalence of these enzymes in clinical Enterobacteriaceae, especially K. pneumoniae and E. coli in China is comparatively lower compared with that of bla SHV -, bla TEM -, bla CTX-M-1 -, bla CTX-M-9 -or bla OXA-1 -encoded enzymes.…”

Section: Introductionmentioning

confidence: 99%

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

et al. 2015

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Resistance to β-lactam antibiotics through β-lactamase production by Enterobacteriaceae continues to burden the health-care sector worldwide. Traditional methods for detection of β-lactamases are time-consuming and labor-intensive and newer methods with varying capabilities continue to be developed. The objective of this study was to develop a multiplex PCR (M-PCR) system for the detection of bla SHV , bla TEM , bla CTX-M-1 , bla CTX-M-9 and bla OXA-1 group genes and to apply it in clinical Klebsiella pneumoniae and Escherichia coli strains. To do this, we used group-specific PCR primers in singleplex reactions followed by optimization into multiplex reactions. Specificity and sensitivity of the M-PCR were then evaluated using 58 reference strains before its application to detect bla group genes in 203 clinical Enterobacteriaceae strains. PCR amplicons were sequenced to determine the β-lactamase subtypes. The M-PCR system exhibited 100% specificity and sensitivity. In all, 83.7% of K. pneumoniae and 89.8% of E. coli clinical strains harbored bla group genes with 46.9%, 40.1%, 15.0%, 21.1% and 6.1% of K. pneumoniae having bla SHV , bla TEM , bla CTX-M-1 , bla CTX-M-9 and bla OXA-1 group genes, respectively, whereas 12.2%, 77.6%, 22.4%, 36.7% and 8.2% of E. coli had bla SHV , bla TEM , bla CTX-M-1 , bla CTX-M-9 and bla OXA-1 group genes, respectively. Bla SHV-1 , bla SHV-11 , bla SHV-27 , bla SHV-33 , bla SHV-144 , bla TEM-1 , bla TEM-135 , bla OXA-1 , bla CTX-M-3 , bla CTX-M-9 , bla CTX-M-14 , bla CTX-M-15 , bla CTX-M-27 , bla CTX-M-55 , bla CTX-M-65 and bla CTX-M-104 were detected. In conclusion, the M-PCR system was efficient and versatile with an advantage of simultaneously detecting all the targeted bla group genes. Hence, it is a potential candidate for developing M-PCR kits for the screening of these genes for clinical or epidemiological purposes.

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Section: Introductionmentioning

confidence: 99%

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

et al. 2015

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“…OXA-10 and -14 -lactamases were purified by anion and cation exchange as previously described (18,20,21). Antimicrobials that were tested included ceftazidime (Glaxo-Wellcome, Stevenage, Hertfordshire, U.K.), ceftriaxone (Roche, Basel, Switzerland), ampicillin sodium, carbenicillin disodium, cephaloridine, cephalothin, cloxacillin, methicillin, oxacillin, and penicillin G (Sigma, St. Louis, MO), aztreonam (Bristol-Myers Squibb AG, Baar, Switzerland), and Meropenem (Zeneca, Basiglio, Italy).…”

Section: Methodsmentioning

confidence: 99%

“…For example, the time course of hydrolysis of some -lactams by OXA-10 -lactamase follows a typical progress curve with many -lactams, but some show more complex curves starting with a hyperstoichiometric burst of hydrolysis that decays to a slower steady-state rate. In contrast, the OXA-14 enzyme has exhibited such complex kinetics with every -lactam tested so far (18,23). It has been suggested that the burst kinetics could be due to interconversion between monomer and dimer forms that have different specific activities, possibly stimulated by reaction with -lactams (24).…”

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Effect of Divalent Metal Cations on the Dimerization of OXA-10 and -14 Class D β-Lactamases from Pseudomonas aeruginosa

et al. 2001

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The factors influencing the oligomerization state of OXA-10 and OXA-14 class D -lactamases in solution have been investigated. Both enzymes were found to exist as an equilibrium mixture of a monomer and dimer, with a K d close to 40 µM. The dimeric form was stabilized by divalent metal cations. The ability of different metal ions to stabilize the dimer was in the following order: Cd 2+ > Cu 2+ > Zn 2+ > Co 2+ > Ni 2+ > Mn 2+ > Ca 2+ > Mg 2+ . The apparent K d s describing the binding of Zn 2+ and Cd 2+ cations to the OXA-10 dimer were 7.8 and 5.7 µM, respectively. The metal ions had a profound effect on the thermal stability of the protein complex observed by differential scanning calorimetry. The enzyme showed a sharp transition with a T m of 58.7°C in the absence of divalent cations, and an equally sharp transition with a T m of 78.4°C in the presence of a saturating concentration of the divalent cation. The thermal transition observed at intermediate concentrations of divalent metal ions was rather broad and lies between these two extremes of temperature. The equilibrium between the monomer and dimer is dependent on pH, and the optimum for the formation of the dimer shifted from pH 6.0 in the absence of divalent cations to pH 7.5 at saturating concentrations. The -lactamase activity increased approximately 2-fold in the presence of saturating concentrations of zinc and cadmium ions. Reaction with -lactams caused a shift in the equilibrium toward monomer formation, and thus an apparent inactivation, but the divalent cations protected against this effect.-Lactams have been the most heavily used antibiotics for the past 50 years (1). Many mechanisms of resistance have been developed by bacteria during this period, including efflux pumps, decreased levels of expression of porins, and modification of the PBPs 1 (penicillin binding proteins, the targets of the -lactam antibiotics), but the most prevalent mechanism is the expression of -lactamases (2). These enzymes inactivate the antibiotics by hydrolyzing the -lactam ring, rendering the antibiotic inactive against PBPs. Four molecular classes of -lactamases exist, A-D (3-5). The class A, C, and D -lactamases are serine hydrolyses, while the class B enzymes are metalloenzymes. The number of known -lactamases has increased rapidly in the past few years with an evolution in the spectrum of activity (penicillinase, extended-spectrum -lactamase, and carbapenemase) that has kept pace with the introduction of new classes of -lactams (6-10). Thus, there has been considerable interest in elucidating the molecular mechanisms of these enzymes to facilitate the design of mechanism-based inhibitors that could be used to rescue the susceptible antibiotics (11).Among the serine -lactamases, the class A and class C enzymes have been extensively studied, whereas relatively little is known about the class D enzymes (11,12). The first structure of a class D enzyme, OXA-10 (PSE-2) -lactamase, has only recently been determined (13,14). Unlike the known enzymes from classes A...

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“…Similarmente às carbapenemases de tipo A, as enzimas de tipo OXAcarbapenemases apresentam resistência às cefalosporinas, monobactâmicos, penicilinas e carbapenêmicos, porém seu substrato preferencial é a oxacilina e são fracamente inibidas pelo ácido clavulânico (Danel et al, 1999 (Poirel et al, 2004c) com alta atividade contra os carbapenêmicos. Essa enzima é codificada por genes inseridos em plasmídio.…”

Section: Oxacilinases De Classe D (Oxa)unclassified

Caracterização molecular da resistência aos carbapenêmicos em enterobactérias isoladas em hospitais brasileiros

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OXA-14, another extended-spectrum variant of OXA-10 (PSE-2) beta-lactamase from Pseudomonas aeruginosa

Cited by 105 publications

References 11 publications

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

Effect of Divalent Metal Cations on the Dimerization of OXA-10 and -14 Class D β-Lactamases from Pseudomonas aeruginosa

Caracterização molecular da resistência aos carbapenêmicos em enterobactérias isoladas em hospitais brasileiros

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