ArticleNature chemical biology2025
Restoring susceptibility to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Outer Membrane-Peptidoglycan Anchoring inJournal of the American Chemical Society · 2026Article
- Exploration of a benzothiophene scaffold for use as adjuvants with β-lactam antibiotics against methicillin-resistantRSC medicinal chemistry · 2026Article
- Phytochemical profiling, metabolomics, and molecular docking studies of Atriplex halimus aerial parts revealing potential insecticidal activity against the malaria vector Anopheles pharoensis.Scientific reports · 2026Article
- Antibiotic resistance genes in companion animals and humans driven by the gut microbial communities: composition, distribution, and implications.BMC veterinary research · 2026Article
- Overcoming Methicillin-ResistantResearch (Washington, D.C.) · 2026Article
- Discovery and Evaluation of a Methylpyrazolopyrimidine Antibacterial Active against Methicillin-ResistantACS infectious diseases · 2025Article
- Chemically tailored anionic antibiotic adjuvants targeting divalent cations to overcome carbapenem resistance in gram-negative bacteria.Science advances · 2025Article
- Trends on Potential Boron-containing Drugs by Advancements in Ligand-protein Crystals Complexes.Current medicinal chemistry · 2025Review
- Activity of Organoboron Compounds against Biofilm-Forming Pathogens.Antibiotics (Basel, Switzerland) · 2024Review
- Forced rewiring of RTK signaling.Nature chemical biology · 2024Article
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19 authors.
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Abstract
Infections by Staphylococcus aureus have been treated historically with β-lactam antibiotics. However, these antibiotics have become obsolete in methicillin-resistant S. aureus by acquisition of the bla and mec operons. The presence of the β-lactam antibiotic is detected by the sensor domains of BlaR and/or MecR, and the information is transmitted to the cytoplasm, resulting in derepression of the antibiotic-resistance genes. We hypothesized that inhibition of the sensor domain would shut down this response system, and β-lactam susceptibility would be restored. An in silico search of 11 million compounds led to a benzimidazole-based hit and, ultimately, to the boronate 4. The X-ray structure of 4 is covalently engaged with the active-site serine of BlaR. Compound 4 potentiates by 16- to 4,096-fold the activities of oxacillin and of meropenem against methicillin-resistant S. aureus strains. The combination of 4 with oxacillin or meropenem shows efficacy in infected mice, validating the strategy.
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