ArticleProceedings of the National Academy of Sciences of the United States of America2018
Directed evolution of multiple genomic loci allows the prediction of antibiotic resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 99 citations in OpenAlex.
- Predicting resistance evolution to guide antibiotic development.Nature reviews. Microbiology · 2026Review
- Probing the limits of genetic recoding using multi-omics-guided evolution.Nature communications · 2026Article
- Decoding efficacy and resistance space at a drug binding site.Nature communications · 2026Article
- Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity.Communications biology · 2025Article
- Exploring antibiotic resistance in diverse homologs of the dihydrofolate reductase protein family through broad mutational scanning.Science advances · 2025Article
- Reviewing the complexities of bacterial biocide susceptibility and in vitro biocide adaptation methodologies.npj antimicrobials and resistance · 2025Review
- ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.Nature microbiology · 2025Article
- Recent Advances in Antimicrobial Resistance: Insights fromMicroorganisms · 2024Review
- ReaL-MGE is a tool for enhanced multiplex genome engineering and application to malonyl-CoA anabolism.Nature communications · 2024Article
- Simultaneous multi-site editing of individual genomes using retron arrays.Nature chemical biology · 2024Article
- Synthetic genomes unveil the effects of synonymous recoding.bioRxiv : the preprint server for biology · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- The Pseudomonas aeruginosa Resistome: Permanent and Transient Antibiotic Resistance, an Overview.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Synthetic directed evolution for targeted engineering of plant traits.Frontiers in plant science · 2024Review
- Metagenomics harvested genus-specific single-stranded DNA-annealing proteins improve and expand recombineering in Pseudomonas species.Nucleic acids research · 2023Article
- Translating eco-evolutionary biology into therapy to tackle antibiotic resistance.Nature reviews. Microbiology · 2023Review
- Article
- Simultaneous multi-site editing of individual genomes using retron arrays.bioRxiv : the preprint server for biology · 2023Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Antibiotic development is frequently plagued by the rapid emergence of drug resistance. However, assessing the risk of resistance development in the preclinical stage is difficult. Standard laboratory evolution approaches explore only a small fraction of the sequence space and fail to identify exceedingly rare resistance mutations and combinations thereof. Therefore, new rapid and exhaustive methods are needed to accurately assess the potential of resistance evolution and uncover the underlying mutational mechanisms. Here, we introduce directed evolution with random genomic mutations (DIvERGE), a method that allows an up to million-fold increase in mutation rate along the full lengths of multiple predefined loci in a range of bacterial species. In a single day, DIvERGE generated specific mutation combinations, yielding clinically significant resistance against trimethoprim and ciprofloxacin. Many of these mutations have remained previously undetected or provide resistance in a species-specific manner. These results indicate pathogen-specific resistance mechanisms and the necessity of future narrow-spectrum antibacterial treatments. In contrast to prior claims, we detected the rapid emergence of resistance against gepotidacin, a novel antibiotic currently in clinical trials. Based on these properties, DIvERGE could be applicable to identify less resistance-prone antibiotics at an early stage of drug development. Finally, we discuss potential future applications of DIvERGE in synthetic and evolutionary biology.
Indexed as
Identifiers
What OpenQuestion holds
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.