ArticleAntimicrobial agents and chemotherapy2005
OXA-46, a new class D beta-lactamase of narrow substrate specificity encoded by a blaVIM-1-containing integron from a Pseudomonas aeruginosa clinical isolate.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Metatranscriptomic time series insight into antibiotic resistance genes and mobile genetic elements in wastewater systems under antibiotic selective pressure.BMC microbiology · 2025Article
- OXA-48-Like β-Lactamases: Global Epidemiology, Treatment Options, and Development Pipeline.Antimicrobial agents and chemotherapy · 2022Review
- Structure-Based Screening of Non-β-Lactam Inhibitors against Class D β-Lactamases: An Approach of Docking and Molecular Dynamics.ACS omega · 2020Article
- Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D β-Lactamase, OXA-436, Found in Isolates from Four Patients at Six Different Hospitals in Denmark.Antimicrobial agents and chemotherapy · 2018Article
- Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Purification and characterization of a new β-lactamase OXA-205 from Pseudomonas aeruginosa.Annals of clinical microbiology and antimicrobials · 2015Article
- Acquired Class D β-Lactamases.Antibiotics (Basel, Switzerland) · 2014Review
- A high-throughput, restriction-free cloning and screening strategy based on ccdB-gene replacement.Microbial cell factories · 2014Article
- OXA-134, a naturally occurring carbapenem-hydrolyzing class D beta-lactamase from Acinetobacter lwoffii.Antimicrobial agents and chemotherapy · 2010Article
- Crystal structure of the narrow-spectrum OXA-46 class D beta-lactamase: relationship between active-site lysine carbamylation and inhibition by polycarboxylates.Antimicrobial agents and chemotherapy · 2010Article
- Genetic and biochemical characterization of TRU-1, the endogenous class C beta-lactamase from Aeromonas enteropelogenes.Antimicrobial agents and chemotherapy · 2010Article
- Penicillin sulfone inhibitors of class D beta-lactamases.Antimicrobial agents and chemotherapy · 2010Article
- Diversity, epidemiology, and genetics of class D beta-lactamases.Antimicrobial agents and chemotherapy · 2010Review
- First countrywide survey of acquired metallo-beta-lactamases in gram-negative pathogens in Italy.Antimicrobial agents and chemotherapy · 2008Article
- Inhibition of OXA-1 beta-lactamase by penems.Antimicrobial agents and chemotherapy · 2008Article
- Insights and inferences about integron evolution from genomic data.BMC genomics · 2008Article
- Modes and modulations of antibiotic resistance gene expression.Clinical microbiology reviews · 2007Review
- Establishing clonal relationships between VIM-1-like metallo-beta-lactamase-producing Pseudomonas aeruginosa strains from four European countries by multilocus sequence typing.Journal of clinical microbiology · 2006Article
- Genetic and biochemical characterization of FUS-1 (OXA-85), a narrow-spectrum class D beta-lactamase from Fusobacterium nucleatum subsp. polymorphum.Antimicrobial agents and chemotherapy · 2006Article
- Molecular investigation of extended-spectrum beta-lactamase genes and potential drug resistance in clinical isolates of Morganella morganii.Annals of Saudi medicineArticle
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant Pseudomonas aeruginosa clinical isolate. The variable region of the integron also contained a bla(VIM-1) metallo-beta-lactamase cassette and a duplicated aacA4 aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D beta-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates of Burkholderia cepacia and in unidentified bacteria from a wastewater plant. Expression of bla(OXA-46) in Escherichia coli decreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced in E. coli and purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D beta-lactamases.
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