ArticleProceedings of the National Academy of Sciences of the United States of America2006
Reducing the fitness cost of antibiotic resistance by amplification of initiator tRNA genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. 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
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
74 citing papers in PubMed, 141 citations in OpenAlex.
- Population size modulates the transition from gene amplification-mediated heteroresistance to stable resistance.npj antimicrobials and resistance · 2026Article
- Experimental Evolution of Yeast Reveals Trade-offs Between Early and Late Stationary Phase.bioRxiv : the preprint server for biology · 2026Article
- Unraveling the Prevalence and Multifaceted Roles of Accessory Peptide Deformylases in Bacterial Adaptation and Resistance.Molecular biology and evolution · 2025Article
- Bacterial peptide deformylase inhibitors induce prophages in competitors.bioRxiv : the preprint server for biology · 2025Article
- Article
- Heteroresistance in Enterobacter cloacae complex caused by variation in transient gene amplification events.npj antimicrobials and resistance · 2025Article
- Recent Advances in Antimicrobial Resistance: Insights fromMicroorganisms · 2024Review
- Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024Review
- Genome engineering on size reduction and complexity simplification: A review.Journal of advanced research · 2024Review
- Article
- Large-scale duplication events underpin population-level flexibility in tRNA gene copy number in Pseudomonas fluorescens SBW25.Nucleic acids research · 2024Article
- Bacteria can compensate the fitness costs of amplified resistance genes via a bypass mechanism.Nature communications · 2024Article
- The Impact of Non-Pathogenic Bacteria on the Spread of Virulence and Resistance Genes.International journal of molecular sciences · 2023Review
- On distinguishing between canonical tRNA genes and tRNA gene fragments in prokaryotes.RNA biology · 2023Article
- Microbial adaptive evolution.Journal of industrial microbiology & biotechnology · 2022Review
- Molecular Characterization ofMicroorganisms · 2022Article
- The Perfect Condition for the Rising of Superbugs: Person-to-Person Contact and Antibiotic Use Are the Key Factors Responsible for the Positive Correlation between Antibiotic Resistance Gene Diversity and Virulence Gene Diversity in Human Metagenomes.Antibiotics (Basel, Switzerland) · 2021Article
- Impact of the gonococcal FC428Emerging microbes & infections · 2020Article
- Suppression of Formylation Provides an Alternative Approach to Vacant Codon Creation in Bacterial In Vitro Translation.Angewandte Chemie (International ed. in English) · 2020Article
- Association of Virulence and Antibiotic Resistance inMicroorganisms · 2020Article
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
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deformylase inhibitors belong to a novel antibiotic class that targets peptide deformylase, a bacterial enzyme that removes the formyl group from N-terminal methionine in nascent polypeptides. Using the bacterium Salmonella enterica, we isolated mutants with resistance toward the peptide deformylase inhibitor actinonin. Resistance mutations were identified in two genes that are required for the formylation of methionyl (Met) initiator tRNA (tRNAi)(fMet): the fmt gene encoding the enzyme methionyl-tRNA formyltransferase and the folD gene encoding the bifunctional enzyme methylenetetrahydrofolate-dehydrogenase and -cyclohydrolase. In the absence of antibiotic, these resistance mutations conferred a fitness cost that was manifested as a reduced growth rate in laboratory medium and in mice. By serially passaging the low-fitness mutants in growth medium without antibiotic, the fitness costs could be partly ameliorated either by intragenic mutations in the fmt/folD genes or by extragenic compensatory mutations. Of the extragenically compensated fmt mutants, approximately one-third carried amplifications of the identical, tandemly repeated metZ and metW genes, encoding tRNAi. The increase in metZW gene copy number varied from 5- to 40-fold and was accompanied by a similar increase in tRNAi levels. The rise in tRNAi level compensated for the lack of methionyl-tRNA formyltransferase activity and allowed translation initiation to proceed with nonformylated methionyl tRNAi. Amplified units varied in size from 1.9 to 94 kbp. Suppression of deleterious mutations by gene amplification may be involved in the evolution of new gene functions.
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.