ArticleJournal of the American Chemical Society2014
Disruption of allosteric response as an unprecedented mechanism of resistance to antibiotics.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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.
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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
44 citing papers in PubMed, 90 citations in OpenAlex.
- Overcoming Ceftaroline Resistance in MRSA Using Ceftaroline-Carbapenem Combination Therapy.Open forum infectious diseases · 2026Article
- Genomic Insights into Multidrug-resistant Mammaliicoccus sciuri Carrying Novel Staphylococcal Cassette Chromosome mec (SCCmec) Elements and Plasmids from Farm Ruminants on the East Coast of Peninsular Malaysia.Current microbiology · 2025Article
- Article
- Structural insights into full-length human fascin1: a target for cancer treatment.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Elucidating allosteric signal disruption in PBP2a: impact of N146K/E150K mutations on ceftaroline resistance in methicillin-resistant Staphylococcus aureus.Journal of computer-aided molecular design · 2025Article
- Isolation and Characterization of Novel Lytic Bacteriophages Infecting Carbapenem-Resistant Pathogenic Diarrheagenic and UropathogenicInfection and drug resistance · 2024Article
- Unraveling the mechanism of ceftaroline-induced allosteric regulation in penicillin-binding protein 2a: insights for novel antibiotic development against methicillin-resistantAntimicrobial agents and chemotherapy · 2023Article
- A Review on Five and Six-Membered Heterocyclic Compounds Targeting the Penicillin-Binding Protein 2 (PBP2A) of Methicillin-ResistantMolecules (Basel, Switzerland) · 2023Review
- Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5.Nature communications · 2023Article
- Prediction of Druggable Allosteric Sites of Undruggable Multidrug Resistance Efflux PumpBiomedical engineering and computational biology · 2023Article
- WYBQ-4: a New Bactericidal Agent against Methicillin-Resistant Staphylococcus aureus.Microbiology spectrum · 2022Article
- The NaHCOAntimicrobial agents and chemotherapy · 2022Article
- Impacts of NaHCOAntibiotics (Basel, Switzerland) · 2022Article
- Molecular docking and proteomics reveals the synergistic antibacterial mechanism of theaflavin with β-lactam antibiotics against MRSA.Frontiers in microbiology · 2022Article
- Evaluation ofIranian journal of microbiology · 2021Article
- Non-Antibiotics (Basel, Switzerland) · 2021Article
- The Role of ArlRS and VraSR in Regulating Ceftaroline Hypersusceptibility in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2021Article
- Mutation-Based Antibiotic Resistance Mechanism in Methicillin-ResistantPharmaceuticals (Basel, Switzerland) · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Unconventional Antibacterials and Adjuvants.Accounts of chemical research · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Ceftaroline, a recently approved β-lactam antibiotic for treatment of infections by methicillin-resistant Staphylococcus aureus (MRSA), is able to inhibit penicillin-binding protein 2a (PBP2a) by triggering an allosteric conformational change that leads to the opening of the active site. The opened active site is now vulnerable to inhibition by a second molecule of ceftaroline, an event that impairs cell-wall biosynthesis and leads to bacterial death. The triggering of the allosteric effect takes place by binding of the first antibiotic molecule 60 Å away from the active site of PBP2a within the core of the allosteric site. We document, by kinetic studies and by determination of three X-ray structures of the mutant variants of PBP2a that result in resistance to ceftaroline, that the effect of these clinical mutants is the disruption of the allosteric trigger in this important protein in MRSA. This is an unprecedented mechanism for antibiotic resistance.
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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.