ArticleProceedings of the National Academy of Sciences of the United States of America2012
Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
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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
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 268 citations in OpenAlex.
- Systematic review of clofazimine for the treatment of drug-resistant tuberculosis.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2013Pooled it
- Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials.British journal of clinical pharmacology · 2017Trial
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- Characterization of Antibiotic-Tolerant Persister Cells inAnimals : an open access journal from MDPI · 2026Article
- Metabolic adaptations in antibiotic-resistantMicrobiology spectrum · 2026Article
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- Reactive oxygen detoxification contributes toeLife · 2026Article
- Implications of bacterial exposure to reactive oxygen and chlorine species.Infection and immunity · 2026Review
- 3‑Methylthiopropionic Acid Kills Carbapenem-ResistantJACS Au · 2026Article
- Usnic Acid Derivatives as Inhibitors ofInternational journal of molecular sciences · 2026Article
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- Sequential eradication of bacterial persisters: integrating phytochemical pharmacology with microenvironment-responsive delivery strategies.Frontiers in microbiology · 2026Review
- Reactive Oxygen Detoxification Contributes tobioRxiv : the preprint server for biology · 2025Article
- Genetic determinants ofMicrobiology spectrum · 2025Article
- Phenolic constituents in pepper (Food chemistry: X · 2025Article
- The Adverse Effects of Tuberculosis Treatment: A Comprehensive Literature Review.Medicina (Kaunas, Lithuania) · 2025Review
- The Role of Hyperbaric Oxygen Therapy in Management of Necrotizing Soft Tissue Infection.Journal of clinical medicine · 2025Review
- Ferroptosis-Like Death Induction inJournal of microbiology and biotechnology · 2025Article
- Deciphering meropenem persistence inAntimicrobial agents and chemotherapy · 2025Article
- Non-Membrane Active Peptide Resensitizes MRSA to β-Lactam Antibiotics and Inhibits S. aureus Virulence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
71 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
5 authors at 4 institutions in 1 country.
Funding
Abstract
During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model capable of yielding a phenotypically antibiotic-tolerant subpopulation of cells, often called persisters, within populations of Mycobacterium smegmatis and M. tuberculosis. We find that persisters are distinct from the larger antibiotic-susceptible population, as a small drop in dissolved oxygen (DO) saturation (20%) allows for their survival in the face of bactericidal antibiotics. In contrast, if high levels of DO are maintained, all cells succumb, sterilizing the culture. With increasing evidence that bactericidal antibiotics induce cell death through the production of reactive oxygen species (ROS), we hypothesized that the drop in DO decreases the concentration of ROS, thereby facilitating persister survival, and maintenance of high DO yields sufficient ROS to kill persisters. Consistent with this hypothesis, the hydroxyl-radical scavenger thiourea, when added to M. smegmatis cultures maintained at high DO levels, rescues the persister population. Conversely, the antibiotic clofazimine, which increases ROS via an NADH-dependent redox cycling pathway, successfully eradicates the persister population. Recent work suggests that environmentally induced antibiotic tolerance of bulk populations may result from enhanced antioxidant capabilities. We now show that the small persister subpopulation within a larger antibiotic-susceptible population also shows differential susceptibility to antibiotic-induced hydroxyl radicals. Furthermore, we show that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections.
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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.