ArticleNature chemical biology2015
Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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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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Who cites it
103 citing papers in PubMed, 165 citations in OpenAlex.
- Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.Molecular biology reports · 2026Review
- Disulfiram reverses fluconazole-resistance mediated by Cdr1 in Candida albicans and interferes with biofilm formation.Applied microbiology and biotechnology · 2026Article
- An Achilles' heel for methicillin-resistantAntimicrobial agents and chemotherapy · 2026Review
- Synergistic Potential of Plant Alkaloids and Intragenic Antimicrobial Peptides in Treating Multidrug-Resistant Infectious Diseases.Antibiotics (Basel, Switzerland) · 2026Article
- Sensitivity profile of tolerant and persistent Staphylococcus spp. from goat mastitis to Jatobá (Hymenaea martiana Hayne) extract.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
- Evolutionary drivers of divergent collateral sensitivity responses during antibiotic therapy.Nature ecology & evolution · 2026Review
- BeyondAntimicrobial agents and chemotherapy · 2026Article
- Synergistic Effects of Thymoquinone, 3-Hydrazinoquinoxaline-2-Thiol, and Amphotericin B Against Methicillin-ResistantInternational journal of general medicine · 2026Article
- Evolutionary trajectories determine feasibility of collateral sensitivity-based antibiotic treatment strategies in critical bacterial pathogens.Communications biology · 2025Article
- Chemically tailored anionic antibiotic adjuvants targeting divalent cations to overcome carbapenem resistance in gram-negative bacteria.Science advances · 2025Article
- Invariant set theory for predicting potential failure of antibiotic cycling.Infectious Disease Modelling · 2025Article
- Unmasking MRSA's Armor: Molecular Mechanisms of Resistance and Pioneering Therapeutic Countermeasures.Microorganisms · 2025Review
- Thymoquinone and 3HQ synergy inhibits CTX-M-15 ESBL.Biomolecules & biomedicine · 2025Article
- Study on collateral sensitivity of tigecycline to colistin-resistantMicrobiology spectrum · 2025Article
- Mechanistic insights into the multitarget synergistic efficacy of farrerol and β-lactam antibiotics in combating methicillin-resistantAntimicrobial agents and chemotherapy · 2025Article
- Unveiling the synergistic power of 3-hydrazinoquinoxaline-2-thiol and vancomycin against MRSA: AnBiomolecules & biomedicine · 2025Article
- A Review Vancomycin Role in Gram Positive Biofilm-Associated Infections: Challenges and Emerging Solutions.Therapeutics and clinical risk management · 2025Review
- Collateral Sensitivity to β-Lactam Antibiotics in Evolved Apramycin-Resistant MRSA.International journal of molecular sciences · 2024Article
- Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis.Nature communications · 2024Article
- Efficacy of aspergillomarasmine A/meropenem combinations with and without avibactam against bacterial strains producing multiple β-lactamases.Antimicrobial agents and chemotherapy · 2024Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple β-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA subspecies N315 and 72 other clinical MRSA isolates in vitro and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents. We demonstrate that these activities also extend to other carbapenem-penicillin-β-lactamase inhibitor combinations. ME/PI/TZ circumvents the tight regulation of the mec and bla operons in MRSA, the basis for inducible resistance to β-lactam antibiotics. Furthermore, ME/PI/TZ subverts the function of penicillin-binding protein-2a (PBP2a) via allostery, which we propose as the mechanism for both synergy and collateral sensitivity. Showing in vivo activity similar to that of linezolid, ME/PI/TZ demonstrates that combinations of older β-lactam antibiotics could be effective against MRSA infections in humans.
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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.