ArticleAntimicrobial agents and chemotherapy2010
Penicillin sulfone inhibitors of class D beta-lactamases.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Tackling the Antibiotic Resistance Caused by Class AInternational journal of molecular sciences · 2018Pooled it
- Characterization of acquired β-lactamases inMicrobiology spectrum · 2024Article
- Redirecting pantoprazole as a metallo-beta-lactamase inhibitor in carbapenem-resistantFrontiers in pharmacology · 2024Article
- A review on the mechanistic details of OXA enzymes of ESKAPE pathogens.Pathogens and global health · 2023Review
- β-lactam Resistance inPathogens (Basel, Switzerland) · 2021Review
- Activity of Imipenem, Meropenem, Cefepime, and Sulbactam in Combination with the β-Lactamase Inhibitor LN-1-255 againstAntibiotics (Basel, Switzerland) · 2021Article
- New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams.International journal of molecular sciences · 2020Review
- Recent advances in the development of β-lactamase inhibitors.Journal of microbiology (Seoul, Korea) · 2020Review
- Broad spectrum antibiotic-degrading metallo-β-lactamases are phylogenetically diverse.Protein & cell · 2020Article
- Identifying Oxacillinase-48 Carbapenemase Inhibitors Using DNA-Encoded Chemical Libraries.ACS infectious diseases · 2020Article
- Structure-Based Screening of Non-β-Lactam Inhibitors against Class D β-Lactamases: An Approach of Docking and Molecular Dynamics.ACS omega · 2020Article
- The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections.Expert opinion on pharmacotherapy · 2019Review
- Therapeutic Efficacy of LN-1-255 in Combination with Imipenem in Severe Infection Caused by Carbapenem-Resistant Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2019Article
- Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent β-Lactam-β-Lactamase Inhibitor Combination.Antimicrobial agents and chemotherapy · 2019Article
- β-lactam/β-lactamase inhibitor combinations: an update.MedChemComm · 2018Review
- Activity of the β-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2017Article
- Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients.ACS infectious diseases · 2017Article
- Effect of the β-Lactamase Inhibitor Vaborbactam Combined with Meropenem against Serine Carbapenemase-Producing Enterobacteriaceae.Antimicrobial agents and chemotherapy · 2016Article
- LN-1-255, a penicillanic acid sulfone able to inhibit the class D carbapenemase OXA-48.The Journal of antimicrobial chemotherapy · 2016Article
- One ring to rule them all: Current trends in combating bacterial resistance to the β-lactams.Protein science : a publication of the Protein Society · 2016Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
OXA beta-lactamases are largely responsible for beta-lactam resistance in Acinetobacter spp. and Pseudomonas aeruginosa, two of the most difficult-to-treat nosocomial pathogens. In general, the beta-lactamase inhibitors used in clinical practice (clavulanic acid, sulbactam, and tazobactam) demonstrate poor activity against class D beta-lactamases. To overcome this challenge, we explored the abilities of beta-lactamase inhibitors of the C-2- and C-3-substituted penicillin and cephalosporin sulfone families against OXA-1, extended-spectrum (OXA-10, OXA-14, and OXA-17), and carbapenemase-type (OXA-24/40) class D beta-lactamases. Three C-2-substituted penicillin sulfone compounds (JDB/LN-1-255, JDB/LN-III-26, and JDB/ASR-II-292) showed low K(i) values for the OXA-1 beta-lactamase (0.70 +/- 0.14 --> 1.60 +/- 0.30 microM) and demonstrated significant K(i) improvements compared to the C-3-substituted cephalosporin sulfone (JDB/DVR-II-214), tazobactam, and clavulanic acid. The C-2-substituted penicillin sulfones JDB/ASR-II-292 and JDB/LN-1-255 also demonstrated low K(i)s for the OXA-10, -14, -17, and -24/40 beta-lactamases (0.20 +/- 0.04 --> 17 +/- 4 microM). Furthermore, JDB/LN-1-255 displayed stoichiometric inactivation of OXA-1 (the turnover number, i.e., the partitioning of the initial enzyme inhibitor complex between hydrolysis and enzyme inactivation [t(n)] = 0) and t(n)s ranging from 5 to 8 for the other OXA enzymes. Using mass spectroscopy to study the intermediates in the inactivation pathway, we determined that JDB/LN-1-255 inhibited OXA beta-lactamases by forming covalent adducts that do not fragment. On the basis of the substrate and inhibitor kinetics of OXA-1, we constructed a model showing that the C-3 carboxylate of JDB/LN-1-255 interacts with Ser115 and Thr213, the R-2 group at C-2 fits between the space created by the long B9 and B10 beta strands, and stabilizing hydrophobic interactions are formed between the pyridyl ring of JDB/LN-1-255 and Val116 and Leu161. By exploiting conserved structural and mechanistic features, JDB/LN-1-255 is a promising lead compound in the quest for effective inhibitors of OXA-type beta-lactamases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.