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Projekt
Bistability in inositol utilization by Salmonella
Antragsteller
Professor Dr. Thilo Martin Fuchs
Fachliche Zuordnung
Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
Förderung
Förderung von 2012 bis 2017
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 218328452
This research project will analyse the population heterogeneity of Salmonella enterica serovar Typhi-murium (S. Typhimurium) during growth with myo-inositol (Ml) as sole carbon and energy source. Hallmarks of S. Typhimurium growth with Ml are two distinct phenotypes, an extended lag phase of two days, the manifestation of hysteresis, stochastic bistability of at least one iol promoter, positive and negative feedback-loops involving the novel inducer ReiD and the repressor lolR, and the influ-ence of external stimuli. Since Ml-utilization contributes to Salmonella virulence, this is a unique ex-ample of a stochastically switching metabolic property linked with bacterial pathogenicity. In close cooperation with TU Braunschweig responsible for mathematical modelling, the following objectives are pursued: Using quantitative growth data of the wildtype and mutants under varying conditions, the key parameters and the dynamic of feedback-loops involved in bistability during Ml degradation will be described (WPI). Salmonella strains with /o/-promoter fusions to fluorescence reporter genes will be analysed on a singlecell level under selected conditions by flow cytometry, and the model derived will be used to predict bistability in vivo (WP2). Following the description of memory development and stability, and its perturbation by selected mutations, the key parameters required for a phenotypic switch between two distinct metabolic states will be defined (WP3). Pilot in vivo experiments in Caenorhabditis elegans and mice will be performed to prove the role of Ml-bistabllity as a successful bet-hedging strategy during Infections (Perspective).
DFG-Verfahren
Schwerpunktprogramme
