ArticleAntimicrobial agents and chemotherapy2016
Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Distribution of DNA gyrase cleavage sites across the Streptococcus pneumoniae genome: relation to transcription and methylation at GATC sites.Nucleic acids research · 2025Article
- Genome-wide antibiotic-CRISPRi profiling identifies LiaR activation as a strategy to resensitize fluoroquinolone-resistant Streptococcus pneumoniae.Nature communications · 2025Article
- Fluoroquinolones for Dermatologists: A Practical Guide to Clinical Use and Risk Management.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The oxidative stress response ofFrontiers in microbiology · 2023Review
- Host Cell Oxidative Stress Promotes Intracellular Fluoroquinolone Persisters of Streptococcus pneumoniae.Microbiology spectrum · 2022Article
- The effect of fluoroquinolones and antioxidans on biofilm formation by Proteus mirabilis strains.Annals of clinical microbiology and antimicrobials · 2022Article
- Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics.The Journal of antibiotics · 2020Article
- The TLR4-MyD88 Signaling Axis Regulates Lung Monocyte Differentiation Pathways in Response toFrontiers in immunology · 2020Article
- Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome.Cell metabolism · 2019Article
- Reactive Oxygen Species Production Is a Major Factor Directing the Postantibiotic Effect of Fluoroquinolones in Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2019Article
- Article
- Fe-S Clusters Emerging as Targets of Therapeutic Drugs.Oxidative medicine and cellular longevity · 2017Review
- Competitive Growth Enhances Conditional Growth Mutant Sensitivity to Antibiotics and Exposes a Two-Component System as an Emerging Antibacterial Target in Burkholderia cenocepacia.Antimicrobial agents and chemotherapy · 2017Article
- Upregulation of the PatAB Transporter Confers Fluoroquinolone Resistance toFrontiers in microbiology · 2017Article
- The Transcriptome ofFrontiers in microbiology · 2017Review
- Cellular Response to Ciprofloxacin in Low-Level Quinolone-ResistantFrontiers in microbiology · 2017Article
- Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications.Oxidative medicine and cellular longevity · 2017Review
- Pyruvate Oxidase as a Critical Link between Metabolism and Capsule Biosynthesis in Streptococcus pneumoniae.PLoS pathogens · 2016Article
- Absence of tmRNA Has a Protective Effect against Fluoroquinolones inFrontiers in microbiology · 2016Article
- Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.PloS one · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction.
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