Modelling and Manipulating the Phagocyte-Mycobacteria Interface

Tuberculosis is the most pervasive infectious disease worldwide, and recent emergence of drug-resistant strains emphasises the need for improved drug treatments. An integrated approach to dissect, model and ultimately manipulate the interactions between mycobacteria and their host is a promising innovative strategy to develop new anti-infective drugs.

Phagocytosis is an ancestral process, and efficient mechanisms of bacteria recognition, engulfment and killing are conserved from free-living amoebae to human macrophages. Intracellular pathogens such as Mycobacterium tuberculosis have evolved specific mechanisms to survive phagocytosis by re-programing phagocytic cells and have thus gained the capacity to replicate intracellularly.

A versatile and powerful host-pathogen model

Dictyostelium discoideum is an amoeba that feeds by phagocytosis and possesses a conserved cellular immunity. It is the target of bacterial pathogens such as Mycobacterium marinum, a widely accepted alternative model for tuberculosis. The genetically tractable D. discoideum – M. marinum infection model provides a powerful system to study mycobacterial pathogenicity. We have used this system in a phenotypic screen to identify anti-infective compounds inhibiting mycobacterial growth in infected cells. Now, we need to identify the mode of action of the compounds and to evaluate their potential as a lead for anti-tubercular drugs.

Innovative methods

We will mainly use dual RNA-sequencing to determine the transcriptional responses of the host and pathogen during infection, as well as the impact of the novel anti-infectives on both. Novel computational methods as well as state-of-the-art network analysis and modelling tools will allow us to predict putative modes of action. The hypotheses will be directly validated using appropriate genetic tools and biological assays.

Principal Investigator Prof. Thierry Soldati; Biochemistry Department, University of Geneva
Involved Institutions University of Zurich, Technische Universität Darmstadt, University of Geneva, SIB Swiss Institute of Bioinformatics
Number of Research Groups 5
Project Duration Mar. 2014 – Feb. 2018
Approved Funds CHF 3 million

Mis à jour en juillet 2014


Prof. Thierry Soldati
Biochemistry Department
University of Geneva
Quai Ernest-Ansermet 30
CH - 1211 Genève 4
phone +44 22 379 64 96

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