ArticleMicrobiology spectrum2022
Development of Resistance to Eravacycline by Klebsiella pneumoniae and Collateral Sensitivity-Guided Design of Combination Therapies.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Resistance of Gram-Negative Bacteria to Eravacycline: A Systematic Review of Data from In Vitro Studies.Pathogens (Basel, Switzerland) · 2025Pooled it
- Predicting resistance evolution to guide antibiotic development.Nature reviews. Microbiology · 2026Review
- Prevalence, mortality, risk factors, and treatment of carbapenem-resistant hypervirulent Klebsiella pneumoniae: an evidence map.Infection · 2026Review
- Eravacycline and omadacycline Rescue multidrug-resistant Elizabethkingia anophelis: Triple-Model evaluation across in Vitro, Galleria mellonella, and murine bacteremia systems.Journal of advanced research · 2026Article
- Eravacycline as a Novel Option for Treating Multidrug-Resistant Gram-Negative and Gram-Positive Bacterial Infections: A Narrative Review.Journal of clinical medicine · 2026Review
- Therapeutic effect of eravacycline against carbapenem-resistant hypervirulentAntimicrobial agents and chemotherapy · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Epidemiology of ESBL-Producing, Carbapenem-Resistant, and Carbapenemase-Producing Enterobacterales in Southern Africa.Antibiotics (Basel, Switzerland) · 2026Review
- Eravacycline monotherapy and combination therapy against KPC-2- and NDM-1-co- producingFrontiers in microbiology · 2026Article
- Eravacycline: evaluation of susceptibility testing methods and activity against multidrug-resistant Enterobacterales and Acinetobacter.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- AMRrounds: susceptibility to the new tetracycline-derivative eravacycline of New Delhi metallo-β-lactamase-producingJAC-antimicrobial resistance · 2025Article
- Evolution and characteristics of tetracycline resistance inMicrobiology spectrum · 2025Article
- Azithromycin represses evolution of ceftazidime/avibactam resistance by translational repression ofJournal of bacteriology · 2025Article
- A Comprehensive Overview of Antibacterial Agents for Combating Multidrug-Resistant Bacteria: The Current Landscape, Development, Future Opportunities, and Challenges.Antibiotics (Basel, Switzerland) · 2025Review
- Emergence of an XDRFrontiers in microbiology · 2025Article
- Screening and comparison ofFrontiers in cellular and infection microbiology · 2025Article
- Dual role ofiMetaOmics · 2024Article
- Collateral Sensitivity to β-Lactam Antibiotics in Evolved Apramycin-Resistant MRSA.International journal of molecular sciences · 2024Article
- Interaction of the Atypical Tetracyclines Chelocardin and Amidochelocardin with Renal Drug Transporters.ACS pharmacology & translational science · 2024Article
- Third-Generation Tetracyclines: Current Knowledge and Therapeutic Potential.Biomolecules · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The evolution of bacterial antibiotic resistance is exhausting the list of currently used antibiotics and endangers those in the pipeline. The combination of antibiotics is a promising strategy that may suppress resistance development and/or achieve synergistic therapeutic effects. Eravacycline is a newly approved antibiotic that is effective against a variety of multidrug-resistant (MDR) pathogens. However, the evolution of resistance to eravacycline and strategies to suppress the evolution remain unexplored. Here, we demonstrated that a carbapenem-resistant Klebsiella pneumoniae clinical isolate quickly developed resistance to eravacycline, which is mainly caused by mutations in the gene encoding the Lon protease. The evolved resistant mutants display collateral sensitivities to β-lactam/β-lactamase inhibitor (BLBLI) combinations aztreonam/avibactam and ceftazidime-avibactam. Proteomic analysis revealed upregulation of the multidrug efflux system AcrA-AcrB-TolC and porin proteins OmpA and OmpU, which contributed to the increased resistance to eravacycline and susceptibility to BLBLIs, respectively. The combination of eravacycline with aztreonam/avibactam or ceftazidime-avibactam suppresses resistance development. We further demonstrated that eravacycline-resistant mutants evolved from an NDM-1-containing K. pneumoniae strain display collateral sensitivity to aztreonam/avibactam, and the combination of eravacycline with aztreonam/avibactam suppresses resistance development. In addition, the combination of eravacycline with aztreonam/avibactam or ceftazidime-avibactam displayed synergistic therapeutic effects in a murine cutaneous abscess model. Overall, our results revealed mechanisms of resistance to eravacycline and collateral sensitivities to BLBLIs and provided promising antibiotic combinations in the treatment of multidrug-resistant K. pneumoniae infections.
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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.