ArticleAntimicrobial agents and chemotherapy2022
Different Conformations Revealed by NMR Underlie Resistance to Ceftazidime/Avibactam and Susceptibility to Meropenem and Imipenem among D179Y Variants of KPC β-Lactamase.
Article in Antimicrobial agents and chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Resistance development in KPC-producingMicrobiology spectrum · 2026Article
- Article
- Emerging resistance to novel β-lactam β-lactamase inhibitor combinations in Klebsiella pneumoniae bearing KPC variants.Journal of global antimicrobial resistance · 2025Article
- Impact of the double deletion ΔG242-T243 in KPC-2 in the effectiveness of ceftazidime-avibactam and imipenem-relebactam.Antimicrobial agents and chemotherapy · 2025Article
- Cefepime-taniborbactam and ceftibuten-ledaborbactam maintain activity against KPC variants that lead to ceftazidime-avibactam resistance.Antimicrobial agents and chemotherapy · 2025Article
- Cefiderocol Resistance Conferred by Plasmid-Located Ferric Citrate Transport System in KPC-Producing Klebsiella pneumoniae.Emerging infectious diseases · 2025Article
- Reversion of KPC-114 to KPC-2 in ceftazidime-avibactam- resistant/meropenem-susceptibleMicrobiology spectrum · 2024Article
- Article
- The mechanism of ceftazidime and cefiderocol hydrolysis by D179Y variants of KPC carbapenemases is similar and involves the formation of a long-lived covalent intermediate.Antimicrobial agents and chemotherapy · 2024Article
- The Effectiveness of Imipenem-Relebactam against Ceftazidime-Avibactam Resistant Variants of the KPC-2 β-Lactamase.Antibiotics (Basel, Switzerland) · 2023Article
- Characterization of a Class A β-Lactamase fromACS bio & med chem Au · 2023Article
- Optimal ceftazidime/avibactam dosing exposure against KPC-producing Klebsiella pneumoniae.The Journal of antimicrobial chemotherapy · 2022Article
- Klebsiella pneumoniae Carbapenemase Variants Resistant to Ceftazidime-Avibactam: an Evolutionary Overview.Antimicrobial agents and chemotherapy · 2022Review
- 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
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
β-Lactamase-mediated resistance to ceftazidime-avibactam (CZA) is a serious limitation in the treatment of Gram-negative bacteria harboring Klebsiella pneumoniae carbapenemase (KPC). Herein, the basis of susceptibility to carbapenems and resistance to ceftazidime (CAZ) and CZA of the D179Y variant of KPC-2 and -3 was explored. First, we determined that resistance to CZA in a laboratory strain of Escherichia coli DH10B was not due to increased expression levels of the variant enzymes, as demonstrated by reverse transcription PCR (RT-PCR). Using timed mass spectrometry, the D179Y variant formed prolonged acyl-enzyme complexes with imipenem (IMI) and meropenem (MEM) in KPC-2 and KPC-3, which could be detected up to 24 h, suggesting that IMI and MEM act as covalent β-lactamase inhibitors more than as substrates for D179Y KPC-2 and -3. This prolonged acyl-enzyme complex of IMI and MEM by D179Y variants was not observed with wild-type (WT) KPCs. CAZ was studied and the D179Y variants also formed acyl-enzyme complexes (1 to 2 h). Thermal denaturation and differential scanning fluorimetry showed that the tyrosine substitution at position 179 destabilized the KPC β-lactamases (KPC-2/3 melting temperature [
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