ArticleEBioMedicine2025
A strategy to re-sensitise drug-resistant Gram-positive bacteria to oxazolidinone-class antibiotics.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Synergistic Effects of Auranofin and Lysozyme Against Staphylococcus Aureus.Probiotics and antimicrobial proteins · 2026Article
- Cefdinir reprograms Gram-positive bacteria to synergize with lysozyme against superbugs.mLife · 2026Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultidrug-resistant bacterial infections have high mortality rates and few treatment options. Synergistic combinations may improve clinical outcome but traditional strategies often damage healthy microbiome. Oxazolidinone-class antibiotics are typical last-resort drugs for treating drug-resistant bacterial infections but are becoming less effective due to resistance development.
methodsAfter high-throughput screening, synergy was further assessed by in vitro indices (like fractional inhibitory concentration index, biofilm formation and resistance development) and in vivo symptoms in animals with skin and ocular bacterial infections (and ocular microbiome extraction analysis). Proteomics, chemical synthesis, multi-microscopy techniques and antibiotic real-time/kinetic accumulation were employed to explore mechanisms and expand translational applications.
findingsCombining phosphorylated oxazolidinone-class antibiotics with positively charged compounds (lysozyme as native representative) resulted in broad-spectrum drug re-sensitisation. In representative combination, urea cycle was disrupted to alkalinise cytoplasm, which subsequently activated alkaline phosphatase to promote conversion of phosphorylated prodrug to active form. By introducing concept of restored healthy microbiome as the evaluated index in antibiotic therapy, we confirmed excellent translational and microbiome-friendly potential of this strategy in clinical settings because it not only inhibited biofilm formation and development of drug-resistant mutations in vitro, but also alleviated symptoms in infected animals including the restoration of healthy microbiome.
interpretationAs both agents have excellent safety profiles, such clinical investigation may immediately be contemplated in humans. Translationally, scientists benefit from strategy by simultaneously achieving greater efficacy (>500-fold re-sensitisation) and higher safety (prodrug-based and microbiome-friendly strategy especially when active form may be toxic).
fundingCollaborative Research Funds from Research Grants Council (C5033-19E).
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