ArticleAntimicrobial agents and chemotherapy2008
In vitro selection and characterization of ceftobiprole-resistant methicillin-resistant Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Unlocking the Bioactive Potential of Streptomyces: A Multidisciplinary Approach to Strain Improvement.MicrobiologyOpen · 2026Review
- Penicillin-Binding Protein-4 (PBP4) ofMicroorganisms · 2026Review
- Marine Bacteria as a Source of Antibiotics AgainstMarine drugs · 2026Review
- Machine learning and cheminformatics-based Identification of lichen-derived compounds targeting mutant PBP4Molecular diversity · 2025Article
- Article
- Article
- In Vitro Antibacterial Activity of Ceftobiprole and Comparator Compounds against Nation-Wide Bloodstream Isolates and Different Sequence Types of MRSA.Antibiotics (Basel, Switzerland) · 2024Article
- Antibiotic Resistance to Molecules Commonly Prescribed for the Treatment of Antibiotic-Resistant Gram-Positive Pathogens: What Is Relevant for the Clinician?Pathogens (Basel, Switzerland) · 2024Review
- Molecular Determinants of β-Lactam Resistance in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2023Review
- Identification ofAntibiotics (Basel, Switzerland) · 2022Article
- Nosocomial Pneumonia in the Era of Multidrug-Resistance: Updates in Diagnosis and Management.Microorganisms · 2021Review
- An experiment-informed signal transduction model for the role of the Staphylococcus aureus MecR1 protein in β-lactam resistance.Scientific reports · 2019Article
- Mechanisms of action and antimicrobial activity of ceftobiprole.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2019Review
- Prevalence and Characterization of Food-Related Methicillin-ResistantFrontiers in microbiology · 2019Article
- Structural and kinetic analyses of penicillin-binding protein 4 (PBP4)-mediated antibiotic resistance inThe Journal of biological chemistry · 2018Article
- High Rate of Ceftobiprole Resistance among Clinical Methicillin-ResistantAntimicrobial agents and chemotherapy · 2018Article
- PBP4 activity and its overexpression are necessary for PBP4-mediated high-level β-lactam resistance.The Journal of antimicrobial chemotherapy · 2018Article
- PBP4 Mediates β-Lactam Resistance by Altered Function.Antimicrobial agents and chemotherapy · 2017Article
- High-Level Resistance of Staphylococcus aureus to β-Lactam Antibiotics Mediated by Penicillin-Binding Protein 4 (PBP4).Antimicrobial agents and chemotherapy · 2017Article
- Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013-2014 at the Geneva University Hospitals.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2017Article
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Authors and funding
5 authors.
Funding
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to beta-lactam antibiotics because it expresses penicillin-binding protein 2a (PBP2a), a low-affinity penicillin-binding protein. An investigational broad-spectrum cephalosporin, ceftobiprole (BPR), binds PBP2a with high affinity and is active against MRSA. We hypothesized that BPR resistance could be mediated by mutations in mecA, the gene encoding PBP2a. We selected BPR-resistant mutants by passage in high-volume broth cultures containing subinhibitory concentrations of BPR. We used strain COLnex (which lacks chromosomal mecA) transformed with pAW8 (a plasmid vector only), pYK20 (a plasmid carrying wild-type mecA), or pYK21 (a plasmid carrying a mutant mecA gene corresponding to five PBP2a mutations). All strains became resistant to BPR by day 9 of passaging, but MICs continued to increase until day 21. MICs increased 256-fold (from 1 to 256 microg/ml) for pAW8, 32-fold (from 4 to 128 microg/ml) for pYK20, and 8-fold (from 16 to 128 mug/ml) for pYK21. Strains carrying wild-type or mutant mecA developed six (pYK20 transformants) or four (pYK21 transformants) new mutations in mecA. The transformation of COLnex with a mecA mutant plasmid conferred BPR resistance, and the loss of mecA converted resistant strains into susceptible ones. Modeling studies predicted that several of the mecA mutations altered BPR binding; other mutations may have mediated resistance by influencing interactions with other proteins. Multiple mecA mutations were associated with BPR resistance in MRSA. BPR resistance also developed in the strain lacking mecA, suggesting a role for chromosomal genes.
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