ArticlePLoS biology2014
Bistable expression of virulence genes in salmonella leads to the formation of an antibiotic-tolerant subpopulation.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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
119 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Molecular Epidemiology and AMR Perspective of Diarrhoeagenic Escherichia coli in Africa: A Systematic Review and Meta-analysis.Journal of epidemiology and global health · 2024Pooled it
- Contributions of persisters and the Eagle effect to survival ofMicrobiology spectrum · 2026Article
- Article
- Metabolic strategies of Enterobacteriaceae gut colonization.Nature reviews. Microbiology · 2026Review
- Characterization of Antibiotic-Tolerant Persister Cells inAnimals : an open access journal from MDPI · 2026Article
- Raman imaging for the investigation of Mycobacterium smegmatis in a mother machine.Analytical and bioanalytical chemistry · 2026Article
- Perturbing H-NS function reveals roles in restricting virulence heterogeneity and pathogen adaptation.PLoS pathogens · 2026Article
- Fast, StreamlinedChemical & biomedical imaging · 2026Article
- Exploring bet-hedging inmSystems · 2026Article
- Glycerol-Driven Energy and Proteostasis Underpin Antibiotic Tolerance inbioRxiv : the preprint server for biology · 2026Article
- Review
- Regulator-derived growth and fitness costs ofbioRxiv : the preprint server for biology · 2026Article
- Perturbing H-NS function reveals roles in restricting virulence heterogeneity and pathogen adaptation.bioRxiv : the preprint server for biology · 2026Article
- Decoding the spatiotemporal heterogeneity of bacterial virulence gene expression using single-cell approaches.Frontiers in microbiology · 2026Review
- Bimodal expression of Type 3 Secretion System 2 enables cooperative virulence among intracellular Salmonella Typhimurium.PLoS pathogens · 2025Article
- Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair.Nature communications · 2025Article
- Article
- Article
- Epigenetic cellular memory inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Yersinia pseudotuberculosis growth arrest during type-III secretion system expression is associated with altered ribosomal protein expression and decreased gentamicin susceptibility.PLoS pathogens · 2025Article
59 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
9 authors.
Funding
Abstract
Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide labor during S. typhimurium infections. Here, we show that heterogeneous virulence gene expression in this organism also promotes survival against exposure to antibiotics through a bet-hedging mechanism. Using microfluidic devices in combination with fluorescence time-lapse microscopy and quantitative image analysis, we analyzed the expression of virulence genes at the single cell level and related it to survival when exposed to antibiotics. We found that, across different types of antibiotics and under concentrations that are clinically relevant, the subpopulation of bacterial cells that express virulence genes shows increased survival after exposure to antibiotics. Intriguingly, there is an interplay between the two consequences of phenotypic heterogeneity. The bet-hedging effect that arises through heterogeneity in virulence gene expression can protect clonal populations against avirulent mutants that exploit and subvert the division of labor within these populations. We conclude that bet-hedging and the division of labor can arise through variation in a single trait and interact with each other. This reveals a new degree of functional complexity of phenotypic heterogeneity. In addition, our results suggest a general principle of how pathogens can evade antibiotics: Expression of virulence factors often entails metabolic costs and the resulting growth retardation could generally increase tolerance against antibiotics and thus compromise treatment.
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.