ArticleThe Journal of antimicrobial chemotherapy2016
LN-1-255, a penicillanic acid sulfone able to inhibit the class D carbapenemase OXA-48.
Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Zwitterionic Penicillin-Derived Sulfone Inhibitor for Combating β-Lactamase-Mediated Antibiotic Resistance.ChemMedChem · 2026Article
- Introducing tetracycline as a potential OXA-48 carbapenemase inhibitor: an in silico and in vitro approach.Scientific reports · 2026Article
- Disarming carbapenemase-producingAntimicrobial agents and chemotherapy · 2026Article
- Enhanced meropenem activity by a microbiome derived peptide targeting oxacillinase 48 carbapenemase in carbapenem resistant Klebsiella pneumoniae isolates.Scientific reports · 2026Article
- Antibacterial activity of enmetazobactam againstAntimicrobial agents and chemotherapy · 2026Article
- Investigating the Effect of Xylitol onInternational journal of microbiology · 2026Article
- Mechanistic basis for inhibition of the extended-spectrum β-lactamase GES-1 by enmetazobactam and tazobactam.FEBS letters · 2025Article
- Advancements in the fight against globally distributed OXA-48 carbapenemase: evaluating the new generation of carbapenemase inhibitors.Antimicrobial agents and chemotherapy · 2025Article
- Novel Penicillin-Based Sulfone-Siderophore Conjugates for Restoring β-Lactam Antibiotic Efficacy.ACS omega · 2024Article
- Interplay between OXA-10 β-Lactamase Production and Low Outer-Membrane Permeability in Carbapenem Resistance in Enterobacterales.Antibiotics (Basel, Switzerland) · 2023Article
- A review on the mechanistic details of OXA enzymes of ESKAPE pathogens.Pathogens and global health · 2023Review
- Review
- Discovery of Quercetin and Its Analogs as Potent OXA-48 Beta-Lactamase Inhibitors.Frontiers in pharmacology · 2022Article
- New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams.International journal of molecular sciences · 2020Review
- Identifying Oxacillinase-48 Carbapenemase Inhibitors Using DNA-Encoded Chemical Libraries.ACS infectious diseases · 2020Article
- Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It.Molecules (Basel, Switzerland) · 2020Review
- Therapeutic Efficacy of LN-1-255 in Combination with Imipenem in Severe Infection Caused by Carbapenem-Resistant Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2019Article
- New Treatment Options against Carbapenem-ResistantAntimicrobial agents and chemotherapy · 2019Review
- Treatment of Infections by OXA-48-Producing Enterobacteriaceae.Antimicrobial agents and chemotherapy · 2018Review
- β-lactam/β-lactamase inhibitor combinations: an update.MedChemComm · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesCarbapenemases are the most important mechanism responsible for carbapenem resistance in Enterobacteriaceae. Among carbapenemases, OXA-48 presents unique challenges as it is resistant to β-lactam inhibitors. Here, we test the capacity of the compound LN-1-255, a 6-alkylidene-2'-substituted penicillanic acid sulfone, to inhibit the activity of the carbapenemase OXA-48.
methodsThe OXA-48 gene was cloned and expressed in Klebsiella pneumoniae and Escherichia coli in order to obtain MICs in the presence of inhibitors (clavulanic acid, tazobactam and sulbactam) and LN-1-255. OXA-48 was purified and steady-state kinetics was performed with LN-1-255 and tazobactam. The covalent binding mode of LN-1-255 with OXA-48 was studied by docking assays.
resultsBoth OXA-48-producing clinical and transformant strains displayed increased susceptibility to carbapenem antibiotics in the presence of 4 mg/L LN-1-255 (2-32-fold increased susceptibility) and 16 mg/L LN-1-255 (4-64-fold increased susceptibility). Kinetic assays demonstrated that LN-1-255 is able to inhibit OXA-48 with an acylation efficiency (k2/K) of 10 ± 1 × 10(4) M(-1) s(-1) and a slow deacylation rate (koff) of 7 ± 1 × 10(-4) s(-1). IC50 was 3 nM for LN-1-255 and 1.5 μM for tazobactam. Lastly, kcat/kinact was 500-fold lower for LN-1-255 than for tazobactam.
conclusionsIn these studies, carbapenem antibiotics used in combination with LN-1-255 are effective against the carbapenemase OXA-48, an important emerging mechanism of antibiotic resistance. This provides an incentive for further investigations to maximize the efficacy of penicillin sulfone inhibition of class D plasmid-carried Enterobacteriaceae carbapenemases.
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