ArticleThe Journal of antimicrobial chemotherapy2014
A kinetic analysis of the inhibition of FOX-4 β-lactamase, a plasmid-mediated AmpC cephalosporinase, by monocyclic β-lactams and carbapenems.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Antibacterial activity of enmetazobactam againstAntimicrobial agents and chemotherapy · 2026Article
- Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2024Review
- Characterization of Two Novel AmpC Beta-Lactamases from the Emerging Opportunistic Pathogen,Antibiotics (Basel, Switzerland) · 2023Article
- Ceftazidime-Avibactam Resistance Mediated by the NAntimicrobial agents and chemotherapy · 2020Article
- Genetics of Acquired Antibiotic Resistance Genes inFrontiers in microbiology · 2020Review
- Structure and Characterization of a Covalent Inhibitor of Src Kinase.Frontiers in molecular biosciences · 2020Article
- Acquisition of Extended-Spectrum β-Lactamase GES-6 Leading to Resistance to Ceftolozane-Tazobactam Combination inAntimicrobial agents and chemotherapy · 2019Article
- LN-1-255, a penicillanic acid sulfone able to inhibit the class D carbapenemase OXA-48.The Journal of antimicrobial chemotherapy · 2016Article
- New β-Lactamase Inhibitors in the Clinic.Infectious disease clinics of North America · 2016Review
- Analysis of the Structure and Function of FOX-4 Cephamycinase.Antimicrobial agents and chemotherapy · 2016Article
- Kinetics of the Interaction between BAL29880 and LK157 and the Class C β-Lactamase CHE-1.Antimicrobial agents and chemotherapy · 2016Article
- In Vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
objectivesClass C β-lactamases are prevalent among Enterobacteriaceae; however, these enzymes are resistant to inactivation by commercially available β-lactamase inhibitors. In order to find novel scaffolds to inhibit class C β-lactamases, the comparative efficacy of monocyclic β-lactam antibiotics (aztreonam and the siderophore monosulfactam BAL30072), the bridged monobactam β-lactamase inhibitor BAL29880, and carbapenems (imipenem, meropenem, doripenem and ertapenem) were tested in kinetic assays against FOX-4, a plasmid-mediated class C β-lactamase (pmAmpC).
methodsThe FOX-4 β-lactamase was purified. Steady-state kinetics, electrospray ionization mass spectrometry (ESI-MS) and ultraviolet difference (UVD) spectroscopy were conducted using the β-lactam scaffolds described.
resultsThe K(i) values for the monocyclic β-lactams against FOX-4 β-lactamase were 0.04 ± 0.01 μM (aztreonam) and 0.66 ± 0.03 μM (BAL30072), and the Ki value for the bridged monobactam BAL29880 was 8.9 ± 0.5 μM. For carbapenems, the Ki values ranged from 0.27 ± 0.05 μM (ertapenem) to 2.3 ± 0.3 μM (imipenem). ESI-MS demonstrated the formation of stable covalent adducts when the monocyclic β-lactams and carbapenems were reacted with FOX-4 β-lactamase. UVD spectroscopy suggested the appearance of different chromophoric intermediates.
conclusionsMonocyclic β-lactam and carbapenem antibiotics are effective mechanism-based inhibitors of FOX-4 β-lactamase, a clinically important pmAmpC, and provide stimulus for the development of new inhibitors to inactivate plasmidic and chromosomal class C β-lactamases.
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