ArticlePloS one2015
Inhibition of Klebsiella β-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review.Infection · 2018Pooled it
- NMR crystallography reveals active-site protonation states of Toho-1 β-lactamase in complex with avibactam.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Resistance development in KPC-producingMicrobiology spectrum · 2026Article
- An integrated computational strategy for profiling terpenoid for dual-target leads against Klebsiella pneumoniae penicillin-binding protein 3 and beta-lactamase.Molecular diversity · 2026Article
- Genomic and molecular characterisation of a KPC-producing Klebsiella pneumoniae clinical isolate resistant to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam.BMC genomic data · 2026Article
- Synergistic Potential of Repurposing non-β-lactam Compounds as Class A serine β-lactamases Inhibitor: Insights from MolecularDocking, Molecular Dynamics Simulations and Antimicrobial Potentiation.Scientific reports · 2026Article
- Structural perspectives on clinical β-lactamase inhibitors: From mechanism to resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Cefepime-taniborbactam and ceftibuten-ledaborbactam maintain activity against KPC variants that lead to ceftazidime-avibactam resistance.Antimicrobial agents and chemotherapy · 2025Article
- Crystal structure of the class A extended-spectrum β-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution.Antimicrobial agents and chemotherapy · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Exploring avibactam and relebactam inhibition ofAntimicrobial agents and chemotherapy · 2023Article
- Resistance to aztreonam-avibactam due to a mutation of SHV-12 in Enterobacter.Annals of clinical microbiology and antimicrobials · 2023Article
- Molecular interaction of a putative inhibitor with bacterial SHV, an enzyme associated with antibiotic resistance.Royal Society open science · 2023Article
- Unveiling the structural features that regulate carbapenem deacylation in KPC-2 through QM/MM and interpretable machine learning.Physical chemistry chemical physics : PCCP · 2023Article
- The role of adjuvants in overcoming antibacterial resistance due to enzymatic drug modification.RSC medicinal chemistry · 2022Review
- Klebsiella pneumoniae Carbapenemase Variants Resistant to Ceftazidime-Avibactam: an Evolutionary Overview.Antimicrobial agents and chemotherapy · 2022Review
- Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-ResistantMicrobiology spectrum · 2022Article
- Structural Characterization of the D179N and D179Y Variants of KPC-2 β-Lactamase: Ω-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam.Antimicrobial agents and chemotherapy · 2022Article
- Biochemical exploration of β-lactamase inhibitors.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
β-Lactamase inhibition is an important clinical strategy in overcoming β-lactamase-mediated resistance to β-lactam antibiotics in Gram negative bacteria. A new β-lactamase inhibitor, avibactam, is entering the clinical arena and promising to be a major step forward in our antibiotic armamentarium. Avibactam has remarkable broad-spectrum activity in being able to inhibit classes A, C, and some class D β-lactamases. We present here structural investigations into class A β-lactamase inhibition by avibactam as we report the crystal structures of SHV-1, the chromosomal penicillinase of Klebsiella pneumoniae, and KPC-2, an acquired carbapenemase found in the same pathogen, complexed with avibactam. The 1.80 Å KPC-2 and 1.42 Å resolution SHV-1 β-lactamase avibactam complex structures reveal avibactam covalently bonded to the catalytic S70 residue. Analysis of the interactions and chair-shaped conformation of avibactam bound to the active sites of KPC-2 and SHV-1 provides structural insights into recently laboratory-generated amino acid substitutions that result in resistance to avibactam in KPC-2 and SHV-1. Furthermore, we observed several important differences in the interactions with amino acid residues, in particular that avibactam forms hydrogen bonds to S130 in KPC-2 but not in SHV-1, that can possibly explain some of the different kinetic constants of inhibition. Our observations provide a possible reason for the ability of KPC-2 β-lactamase to slowly desulfate avibactam with a potential role for the stereochemistry around the N1 atom of avibactam and/or the presence of an active site water molecule that could aid in avibactam desulfation, an unexpected consequence of novel inhibition chemistry.
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