ArticlePLoS pathogens2016
A Precise Temperature-Responsive Bistable Switch Controlling Yersinia Virulence.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Decoding the spatiotemporal heterogeneity of bacterial virulence gene expression using single-cell approaches.Frontiers in microbiology · 2026Review
- T6SS4 is heterogeneously expressed in Yersinia pseudotuberculosis and is a target for transcriptional and post-transcriptional regulation.PLoS pathogens · 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
- Detection of virulence factors in opportunistic bacteria: advances, challenges, and practical implementation.Frontiers in microbiology · 2025Review
- Development of an inducer-free, virulence gene promoter-controlled, and fluorescent reporter-labeled CRISPR interference system inMicrobiology spectrum · 2024Article
- Single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities.Communications biology · 2024Article
- A ParDE toxin-antitoxin system is responsible for the maintenance of theFrontiers in cellular and infection microbiology · 2023Article
- Navigating Environmental Transitions: the Role of Phenotypic Variation in Bacterial Responses.mBio · 2022Review
- Stochastic activation of a family of TetR type transcriptional regulators controls phenotypic heterogeneity inPNAS nexus · 2022Article
- Waddington's Landscapes in the Bacterial World.Frontiers in microbiology · 2021Review
- For the Greater (Bacterial) Good: Heterogeneous Expression of Energetically Costly Virulence Factors.Infection and immunity · 2020Review
- The Yersinia pseudotuberculosis Cpx envelope stress system contributes to transcriptional activation of rovM.Virulence · 2019Article
- Cell-length heterogeneity: a population-level solution to growth/virulence trade-offs in the plant pathogen Dickeya dadantii.PLoS pathogens · 2019Article
- One for All, but Not All for One: Social Behavior during Bacterial Diseases.Trends in microbiology · 2019Review
- Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency.PLoS pathogens · 2018Article
- Discovering RNA-Based Regulatory Systems forFrontiers in cellular and infection microbiology · 2018Review
- AllFrontiers in cellular and infection microbiology · 2018Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Different biomolecules have been identified in bacterial pathogens that sense changes in temperature and trigger expression of virulence programs upon host entry. However, the dynamics and quantitative outcome of this response in individual cells of a population, and how this influences pathogenicity are unknown. Here, we address these questions using a thermosensing virulence regulator of an intestinal pathogen (RovA of Yersinia pseudotuberculosis) as a model. We reveal that this regulator is part of a novel thermoresponsive bistable switch, which leads to high- and low-invasive subpopulations within a narrow temperature range. The temperature range in which bistability is observed is defined by the degradation and synthesis rate of the regulator, and is further adjustable via a nutrient-responsive regulator. The thermoresponsive switch is also characterized by a hysteretic behavior in which activation and deactivation occurred on vastly different time scales. Mathematical modeling accurately mirrored the experimental behavior and predicted that the thermoresponsiveness of this sophisticated bistable switch is mainly determined by the thermo-triggered increase of RovA proteolysis. We further observed RovA ON and OFF subpopulations of Y. pseudotuberculosis in the Peyer's patches and caecum of infected mice, and that changes in the RovA ON/OFF cell ratio reduce tissue colonization and overall virulence. This points to a bet-hedging strategy in which the thermoresponsive bistable switch plays a key role in adapting the bacteria to the fluctuating conditions encountered as they pass through the host's intestinal epithelium and suggests novel strategies for the development of antimicrobial therapies.
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