ArticleCommunications biology2021
Potentiating antibiotic efficacy via perturbation of non-essential gene expression.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A comprehensive review of cluster methods for drug-drug interaction network.Quantitative biology (Beijing, China) · 2026Review
- Bioinformatic evaluation of ClpP as a vaccine target in Streptococcus pneumoniae.Biotechnology letters · 2026Article
- Developing antisense oligomer biotics "asobiotics" as precision antibacterials: designs, strategies, and considerations for future success.FEMS microbiology reviews · 2026Review
- Evaluating the predictive power of combined gene expression dynamics from single cells on antibiotic survival.mSystems · 2025Article
- Antibiotic potentiators as a promising strategy for combating antibiotic resistance.npj antimicrobials and resistance · 2025Review
- A hybrid machine learning model with attention mechanism and multidimensional multivariate feature coding for essential gene prediction.BMC biology · 2025Article
- RNA toehold switch-based reporter assay to assess bacterial uptake of antisense oligomers.mBio · 2025Article
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- Maintenance of bacterial outer membrane lipid asymmetry: insight into MlaA.BMC microbiology · 2024Review
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- Synergistic Effect of SOS Response and GATC Methylome Suppression on Antibiotic Stress Survival in Escherichia coli.Antimicrobial agents and chemotherapy · 2023Article
- A Library of Promoter-Applied and environmental microbiology · 2023Article
- Inhibitors ofPharmaceuticals (Basel, Switzerland) · 2022Article
- Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Proliferation of multidrug-resistant (MDR) bacteria poses a threat to human health, requiring new strategies. Here we propose using fitness neutral gene expression perturbations to potentiate antibiotics. We systematically explored 270 gene knockout-antibiotic combinations in Escherichia coli, identifying 90 synergistic interactions. Identified gene targets were subsequently tested for antibiotic synergy on the transcriptomic level via multiplexed CRISPR-dCas9 and showed successful sensitization of E. coli without a separate fitness cost. These fitness neutral gene perturbations worked as co-therapies in reducing a Salmonella enterica intracellular infection in HeLa. Finally, these results informed the design of four antisense peptide nucleic acid (PNA) co-therapies, csgD, fnr, recA and acrA, against four MDR, clinically isolated bacteria. PNA combined with sub-minimal inhibitory concentrations of trimethoprim against two isolates of Klebsiella pneumoniae and E. coli showed three cases of re-sensitization with minimal fitness impacts. Our results highlight a promising approach for extending the utility of current antibiotics.
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