A precise temperature-responsive bistable switch controlling yersinia virulence

Autor: Louisa Roselius, Aaron M. Nuss, Petra Dersch, René Bücker, Ann Kathrin Heroven, Katharina Herbst, Johannes Müller, Christoph Wittmann, Franziska Schuster, Johannes Klein, Richard Münch, Fabio Pisano, Dieter Jahn
Přispěvatelé: Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Bistability
Molecular biology
Regulator
Yersinia pseudotuberculosis Infections
Electrophoretic Mobility Shift Assay
Yersinia
Pathology and Laboratory Medicine
Cell Fusion
Peyer's Patches
Mice
Fluorescence Microscopy
Spectrum Analysis Techniques
Medicine and Health Sciences
Yersinia pseudotuberculosis
Biology (General)
Pathogen
education.field_of_study
Microscopy
Mice
Inbred BALB C
biology
Virulence
Temperature
Light Microscopy
Flow Cytometry
Intestinal epithelium
Cell biology
Bacterial Pathogens
Medical Microbiology
Spectrophotometry
Female
Cytophotometry
Pathogens
Anatomy
Research Article
Cell Physiology
QH301-705.5
Virulence Factors
030106 microbiology
Immunology
Population
Blotting
Western
DNA construction
Microbiology
Time-Lapse Imaging
Yersinia Pseudotuberculosis
Lymphatic System
03 medical and health sciences
Bacterial Proteins
Virology
Genetics
Animals
education
Microbial Pathogens
Bacteria
Organisms
Biology and Life Sciences
Cell Biology
RC581-607
biology.organism_classification
Research and analysis methods
Gastrointestinal Tract
Disease Models
Animal
030104 developmental biology
Molecular biology techniques
Plasmid Construction
Parasitology
Immunologic diseases. Allergy
Digestive System
Transcription Factors
Zdroj: PLoS Pathog. 12:e1006091 (2016)
PLoS Pathogens
PLoS Pathogens, Vol 12, Iss 12, p e1006091 (2016)
Popis: 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.
Author Summary The ability of pathogens to sense temperature changes when they enter their mammalian hosts from the environment is crucial to optimize their fitness and adjust expression of their virulence programs. Until now it has been assumed that all cells within a population participate in the thermo-triggered adaptive response. Here, we show that a small subpopulation of an enteric pathogen does not follow thermo-induced reprogramming when the bacteria pass the intestinal epithelial layer. Observed heterogeneity is promoted by a new type of bistable switch, implicating a highly precise, thermoresponsive control element. Moreover, we demonstrate that this regulatory implement is important for virulence as it prepares the pathogen for sudden, unpredictable fluctuations encountered during host entry and exit.
Databáze: OpenAIRE
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