ArticleGenetics2009
Contribution of gene amplification to evolution of increased antibiotic resistance in Salmonella typhimurium.
Article in Genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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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.
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Who cites it
74 citing papers in PubMed, 116 citations in OpenAlex.
- Population size modulates the transition from gene amplification-mediated heteroresistance to stable resistance.npj antimicrobials and resistance · 2026Article
- Cobalt and nickel ion synergy promotes gene amplification and stable metal resistance inApplied and environmental microbiology · 2026Article
- Non-canonical gene amplifications facilitate adaptive evolution in bacteria.Nature microbiology · 2026Article
- Resistance potentiators: Evolutionary catalysts of antibiotic resistance.PLoS biology · 2026Article
- Article
- Colistin heteroresistance, mechanisms, diagnostic methods, and therapeutic options: A review.Germs · 2025Review
- Antibiotic-induced stress responses in Gram-negative bacteria and their role in antibiotic resistance.The Journal of antimicrobial chemotherapy · 2025Review
- Article
- Insights into antibiotic resistance promoted by quinolone exposure.Antimicrobial agents and chemotherapy · 2025Article
- Epidemiology, mechanisms, and clinical impact of bacterial heteroresistance.npj antimicrobials and resistance · 2025Review
- Recent Advances in Antimicrobial Resistance: Insights fromMicroorganisms · 2024Review
- Evolution of extended-spectrum β-lactamase-producing ST131 Escherichia coli at a single hospital over 15 years.Scientific reports · 2024Article
- ISmBio · 2024Article
- Generation and maintenance of the circularized multimeric IS26-associated translocatable unit encoding multidrug resistance.Communications biology · 2024Article
- Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria.Nature communications · 2024Article
- Duplicated antibiotic resistance genes reveal ongoing selection and horizontal gene transfer in bacteria.Nature communications · 2024Article
- Evolution of extended-spectrum β-lactamase-producing ST131bioRxiv : the preprint server for biology · 2023Article
- The Dynamic Fungal Genome: Polyploidy, Aneuploidy and Copy Number Variation in Response to Stress.Annual review of microbiology · 2023Review
- Combatting persister cells: The daunting task in post-antibiotics era.Cell insight · 2023Review
- Cultivating antimicrobial resistance: how intensive agriculture ploughs the way for antibiotic resistance.Microbiology (Reading, England) · 2023Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of beta-lactam antibiotics has led to the evolution and global spread of a variety of resistance mechanisms, including beta-lactamases, a group of enzymes that degrade the beta-lactam ring. The evolution of increased beta-lactam resistance was studied by exposing independent lineages of Salmonella typhimurium to progressive increases in cephalosporin concentration. Each lineage carried a beta-lactamase gene (bla(TEM-1)) that provided very low resistance. In most lineages, the initial response to selection was an amplification of the bla(TEM-1) gene copy number. Amplification was followed in some lineages by mutations (envZ, cpxA, or nmpC) that reduced expression of the uptake functions, the OmpC, OmpD, and OmpF porins. The initial resistance provided by bla(TEM-1) amplification allowed the population to expand sufficiently to realize rare secondary point mutations. Mathematical modeling showed that amplification often is likely to be the initial response because events that duplicate or further amplify a gene are much more frequent than point mutations. These models show the importance of the population size to appearance of later point mutations. Transient gene amplification is likely to be a common initial mechanism and an intermediate in stable adaptive improvement. If later point mutations (allowed by amplification) provide sufficient adaptive improvement, the amplification may be lost.
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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.