ArticleNature communications2024
Beta-lactamase dependent and independent evolutionary paths to high-level ampicillin resistance.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Population size modulates the transition from gene amplification-mediated heteroresistance to stable resistance.npj antimicrobials and resistance · 2026Article
- Selective context, rather than persister cycling alone, drives resistance fixation in Escherichia coli.npj antimicrobials and resistance · 2026Article
- Mutations in RNA polymerase that drive the emergence of antibiotic resistance.Current opinion in microbiology · 2026Review
- Non-canonical gene amplifications facilitate adaptive evolution in bacteria.Nature microbiology · 2026Article
- Contributions of intra- and extracellular antibiotic degradation to collective [Formula: see text]-lactam survival.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pharmacokinetics of Long-Acting Ampicillin and Its Impact on the Gut Microbiome and Resistome in Rhesus Macaques (Macaca mulatta).Journal of veterinary pharmacology and therapeutics · 2026Article
- Comparative study of piperacillin-tazobactam versus ampicillin in the treatment of severe pneumonia in children: A retrospective study.Medicine · 2026Article
- Harnessing Nature's Algorithm: From Test Tubes to Autonomous In Vivo Evolution.Biotechnology journal · 2026Review
- Novel continuous experimental evolution methodology uncovers rapid resistance development and cross-resistance.npj antimicrobials and resistance · 2026Article
- Fitness costs and persistence of plasmid-mediated cephalosporin resistance inFrontiers in microbiology · 2026Review
- Hitchhiking genes and boundaries of AmpC amplicons during amoxicillin resistance development in E. coli.BMC microbiology · 2025Article
- Review
- Driving factors for beta-lactam resistance gene amplification duringAntimicrobial agents and chemotherapy · 2025Article
- Antechodynamics and Antechokinetics: Dynamics and Kinetics of Antibiotic Resistance Biomolecules.Biomolecules · 2025Review
- Tripartite Loops Reverse Antibiotic Resistance.Molecular biology and evolution · 2025Article
- Ceftazidime-avibactam use selects multidrug-resistance and prevents designing collateral sensitivity-based therapies against Pseudomonas aeruginosa.Nature communications · 2025Article
- Progression ofmBio · 2025Article
- Genetic adaptation to amoxicillin in Escherichia coli: The limited role of dinB and katE.PloS one · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The incidence of beta-lactam resistance among clinical isolates is a major health concern. A key method to study the emergence of antibiotic resistance is adaptive laboratory evolution. However, in the case of the beta-lactam ampicillin, bacteria evolved in laboratory settings do not recapitulate clinical-like resistance levels, hindering efforts to identify major evolutionary paths and their dependency on genetic background. Here, we used the Microbial Evolution and Growth Arena (MEGA) plate to select ampicillin-resistant Escherichia coli mutants with varying degrees of resistance. Whole-genome sequencing of resistant isolates revealed that ampicillin resistance was acquired via a combination of single-point mutations and amplification of the gene encoding beta-lactamase AmpC. However, blocking AmpC-mediated resistance revealed latent adaptive pathways: strains deleted for ampC were able to adapt through combinations of changes in genes involved in multidrug resistance encoding efflux pumps, transcriptional regulators, and porins. Our results reveal that combinations of distinct genetic mutations, accessible at large population sizes, can drive high-level resistance to ampicillin even independently of beta-lactamases.
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