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Nuss, A.M.* ; Schuster, F.* ; Roselius, L.* ; Klein, J.* ; Bücker, R.* ; Herbst, K.* ; Heroven, A.K.* ; Pisano, F.* ; Wittmann, C.* ; Münch, R.* ; Müller, J. ; Jahn, D.* ; Dersch, P.*

A precise temperature-responsive bistable switch controlling yersinia virulence.

PLoS Pathog. 12:e1006091 (2016)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Phenotypic Heterogeneity; Pseudotuberculosis; Invasin; Bacteria; Infection; Rova; Mice; Individuality; Bistability; Salmonella
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Zeitschrift PLoS Pathogens
Quellenangaben Band: 12, Heft: 12, Seiten: , Artikelnummer: e1006091 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort San Francisco
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-001
PubMed ID 28006011
DOI 10.1371/journal.ppat.1006091
WOS ID WOS:000392202100058
Scopus ID 85008199459
Erfassungsdatum 2016-12-31
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