ArticleProceedings of the National Academy of Sciences of the United States of America2013
Molecular mechanisms of multiple toxin-antitoxin systems are coordinated to govern the persister phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
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
70 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- A Systematic Overview of Type II and III Toxin-Antitoxin Systems with a Focus on Druggability.Toxins · 2018Pooled it
- Tail-specific protease (Tsp)-mediated envelope remodeling and beta-lactam tolerance inMicrobiology spectrum · 2026Article
- Beyond metabolic dormancy: metabolic rewiring in bacterial persistence.Nature communications · 2026Review
- Article
- Bistability in type I toxin-antitoxin systems may lead to stress-induced persister formation.NPJ systems biology and applications · 2025Article
- Toxin-antitoxins and sigma factors may optimize the fitness of free-living bacteria throughout the life cycle via an integrated nutrient-responsive cybernetic system.Journal of the Royal Society, Interface · 2025Review
- Adaptive Resistance ofMicroorganisms · 2025Article
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
- HigA2 (Rv2021c) Is a Transcriptional Regulator with Multiple Regulatory Targets inMicroorganisms · 2024Article
- Leveraging Cancer Phenotypic Plasticity for Novel Treatment Strategies.Journal of clinical medicine · 2024Article
- Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update.British journal of biomedical science · 2024Review
- Impact of Genomic Deletion RD16 on the Expression of theCurrent issues in molecular biology · 2023Article
- Bacterial toxin-antitoxin systems: Novel insights on toxin activation across populations and experimental shortcomings.Current research in microbial sciences · 2023Review
- Comparative analysis of five type II TA systems identified inFrontiers in cellular and infection microbiology · 2023Article
- The High Mutational Sensitivity of ccdA Antitoxin Is Linked to Codon Optimality.Molecular biology and evolution · 2022Article
- Integrative biology of persister cell formation: molecular circuitry, phenotypic diversification and fitness effects.Journal of the Royal Society, Interface · 2022Review
- Comparative Analysis of Diverse Acetyltransferase-Type Toxin-Antitoxin Loci in Klebsiella pneumoniae.Microbiology spectrum · 2022Article
- A minimal model for gene expression dynamics of bacterial type II toxin-antitoxin systems.Scientific reports · 2021Article
- Impacts of type II toxin-antitoxin systems on cell physiology and environmental behavior in acetic acid bacteria.Applied microbiology and biotechnology · 2021Review
10 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
2 authors.
Funding
Abstract
Toxin-antitoxin systems are ubiquitous and have been implicated in persistence, the multidrug tolerance of bacteria, biofilms, and, by extension, most chronic infections. However, their purpose, apparent redundancy, and coordination remain topics of debate. Our model relates molecular mechanisms to population dynamics for a large class of toxin-antitoxin systems and suggests answers to several of the open questions. The generic architecture of toxin-antitoxin systems provides the potential for bistability, and even when the systems do not exhibit bistability alone, they can be coupled to create a strongly bistable, hysteretic switch between normal and toxic states. Stochastic fluctuations can spontaneously switch the system to the toxic state, creating a heterogeneous population of growing and nongrowing cells, or persisters, that exist under normal conditions, rather than as an induced response. Multiple toxin-antitoxin systems can be cooperatively marshaled for greater effect, with the dilution determined by growth rate serving as the coordinating signal. The model predicts and elucidates experimental results that show a characteristic correlation between persister frequency and the number of toxin-antitoxin systems.
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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.