ArticleProceedings of the National Academy of Sciences of the United States of America2025
Large-scale combination screens reveal small-molecule sensitization of antibiotic-resistant gram-negative ESKAPE pathogens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Macrolide antibiotic action, resistance, and tolerance, and approaches to improve their activity against Gram-negative bacteria.The Journal of antibiotics · 2026Review
- Article
- Enhancing the Antimicrobial Potency of Self-Assembling Antibiotics by Co-Assembly-Based Aggregation Modulation.Macromolecular bioscience · 2026Article
- Molecular mechanism of action of small molecule SMT-738 on bacterial lipoprotein transporter LolCDE.Nature communications · 2026Article
- Droplet microfluidics strategies for overcoming bottlenecks in antibiotics discovery.iScience · 2026Review
- Loss of essential outer membrane functions causes drug hypersensitization inbioRxiv : the preprint server for biology · 2025Article
- Bacterial peptide deformylase inhibitors induce prophages in competitors.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
25 authors.
Funding
Abstract
Antibiotic resistance, especially in multidrug-resistant ESKAPE pathogens, remains a worldwide problem. Combination antimicrobial therapies may be an important strategy to overcome resistance and broaden the spectrum of existing antibiotics. However, this strategy is limited by the ability to efficiently screen large combinatorial chemical spaces. Here, we deployed a high-throughput combinatorial screening platform, DropArray, to evaluate the interactions of over 30,000 compounds with up to 22 antibiotics and 6 strains of gram-negative ESKAPE pathogens, totaling to over 1.3 million unique strain-antibiotic-compound combinations. In this dataset, compounds more frequently exhibited synergy with known antibiotics than single-agent activity. We identified a compound, P2-56, and developed a more potent analog, P2-56-3, which potentiated rifampin (RIF) against antibiotic-resistant strains of
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