2.50
Hdl Handle:
http://hdl.handle.net/10033/620727
Title:
A Precise Temperature-Responsive Bistable Switch Controlling Yersinia Virulence.
Authors:
Nuss, Aaron Mischa; Schuster, Franziska; Roselius, Louisa; Klein, Johannes; Bücker, René; Herbst, Katharina; Heroven, Ann Kathrin; Pisano, Fabio; Wittmann, Christoph; Münch, Richard; Müller, Johannes; Jahn, Dieter; Dersch, Petra ( 0000-0001-8177-3280 )
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
A Precise Temperature-Responsive Bistable Switch Controlling Yersinia Virulence. 2016, 12 (12):e1006091 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Dec-2016
URI:
http://hdl.handle.net/10033/620727
DOI:
10.1371/journal.ppat.1006091
PubMed ID:
28006011
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the research group immunoregulation (IREG)

Full metadata record

DC FieldValue Language
dc.contributor.authorNuss, Aaron Mischaen
dc.contributor.authorSchuster, Franziskaen
dc.contributor.authorRoselius, Louisaen
dc.contributor.authorKlein, Johannesen
dc.contributor.authorBücker, Renéen
dc.contributor.authorHerbst, Katharinaen
dc.contributor.authorHeroven, Ann Kathrinen
dc.contributor.authorPisano, Fabioen
dc.contributor.authorWittmann, Christophen
dc.contributor.authorMünch, Richarden
dc.contributor.authorMüller, Johannesen
dc.contributor.authorJahn, Dieteren
dc.contributor.authorDersch, Petraen
dc.date.accessioned2017-01-18T15:08:42Z-
dc.date.available2017-01-18T15:08:42Z-
dc.date.issued2016-12-
dc.identifier.citationA Precise Temperature-Responsive Bistable Switch Controlling Yersinia Virulence. 2016, 12 (12):e1006091 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid28006011-
dc.identifier.doi10.1371/journal.ppat.1006091-
dc.identifier.urihttp://hdl.handle.net/10033/620727-
dc.description.abstractDifferent 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleA Precise Temperature-Responsive Bistable Switch Controlling Yersinia Virulence.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPLoS pathogensen
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