ArticlemBio2013
Clinically relevant mutant DNA gyrase alters supercoiling, changes the transcriptome, and confers multidrug resistance.
Article in mBio, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 96 citations in OpenAlex.
- ISEmerging microbes & infections · 2026Article
- SOS-mediated prophage induction constrains resistance evolution to DNA-damaging antibiotics.bioRxiv : the preprint server for biology · 2026Article
- Cinnamic-Hydroxamic-Acid Derivatives Exhibit Antibiotic, Anti-Biofilm, and Supercoiling Relaxation Properties by Targeting Bacterial Nucleoid-Associated Protein HU.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Novel Metabolites ofJournal of fungi (Basel, Switzerland) · 2026Article
- Emergence of supercoiling-mediated regulatory networks through the evolution of bacterial chromosome organization.PLoS computational biology · 2025Article
- Antibiotic resistance begets more resistance: chromosomal resistance mutations mitigate fitness costs conferred by multi-resistant clinical plasmids.Microbiology spectrum · 2024Article
- Evolution of triclosan resistance modulates bacterial permissiveness to multidrug resistance plasmids and phages.Nature communications · 2024Article
- Reactive oxygen species accelerateiScience · 2023Article
- DNA supercoiling and regulation of intrinsic β-lactamase in pathogenic Escherichia coli.Archives of microbiology · 2023Review
- Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes.Molecular biology and evolution · 2023Article
- Disrupting the ArcA Regulatory Network Amplifies the Fitness Cost of Tetracycline Resistance in Escherichia coli.mSystems · 2023Article
- Plasticity and Stereotypic Rewiring of the Transcriptome Upon Bacterial Evolution of Antibiotic Resistance.Molecular biology and evolution · 2023Article
- Environmental complexity is more important than mutation in driving the evolution of latent novel traits in E. coli.Nature communications · 2022Article
- Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance.Clinical microbiology reviews · 2022Review
- Article
- Quantitative contribution of the spacer length in the supercoiling-sensitivity of bacterial promoters.Nucleic acids research · 2022Article
- Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone resistance evolution.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Multiple Novel Traits without Immediate Benefits Originate in Bacteria Evolving on Single Antibiotics.Molecular biology and evolution · 2022Article
- Combining transposon mutagenesis and reporter genes to identify novel regulators of the topA promoter in Streptomyces.Microbial cell factories · 2021Article
- Mutant RNA polymerase can reduce susceptibility to antibiotics via ppGpp-independent induction of a stringent-like response.The Journal of antimicrobial chemotherapy · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledBacterial DNA is maintained in a supercoiled state controlled by the action of topoisomerases. Alterations in supercoiling affect fundamental cellular processes, including transcription. Here, we show that substitution at position 87 of GyrA of Salmonella influences sensitivity to antibiotics, including nonquinolone drugs, alters global supercoiling, and results in an altered transcriptome with increased expression of stress response pathways. Decreased susceptibility to multiple antibiotics seen with a GyrA Asp87Gly mutant was not a result of increased efflux activity or reduced reactive-oxygen production. These data show that a frequently observed and clinically relevant substitution within GyrA results in altered expression of numerous genes, including those important in bacterial survival of stress, suggesting that GyrA mutants may have a selective advantage under specific conditions. Our findings help contextualize the high rate of quinolone resistance in pathogenic strains of bacteria and may partly explain why such mutant strains are evolutionarily successful. IMPORTANCE: Fluoroquinolones are a powerful group of antibiotics that target bacterial enzymes involved in helping bacteria maintain the conformation of their chromosome. Mutations in the target enzymes allow bacteria to become resistant to these antibiotics, and fluoroquinolone resistance is common. We show here that these mutations also provide protection against a broad range of other antimicrobials by triggering a defensive stress response in the cell. This work suggests that fluoroquinolone resistance mutations may be beneficial under a range of conditions.
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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.