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Talk by Thierry Soldati
Thierry Soldati
Title: "Role of membrane microdomain in phagocytosis and intracellular infections by mycobacteria"
Occasion: SFB Seminar
Host: Caroline Barisch
Start: 30.06.2022 - 16:15
Location: CellNanOs 38/201
About the speaker: Prof. Thierry Soldati heads a research group in the renowned Biochemistry Department at the University of Geneva.
Abstract of the talk: Mycobacterium marinum and Mycobacterium tuberculosis are genetically close relatives and share common virulence factors and a remarkably similar infectious cycle. Dictyostelium discoideum is a social amoeba that shares many cell-autonomous defence pathways with immune phagocytes and is a powerful alternative host model for mycobacteria infections. The metazoan flotillins are lipid rafts residents involved in membrane trafficking and recycling of plasma membrane proteins. D. discoideum possesses three flotillin-like vacuolins, VacA, B and C. All three, like flotillins, are strongly associated with membranes and partly with lipid rafts and are strictly required for uptake of various particles by phagocytosis. During infection of D. discoideum with M. marinum, VacC was specifically and highly induced and all three vacuolin isoforms were enriched at the mycobacteria-containing-vacuole (MCV). In addition, absence of vacuolins reduced escape from the MCV and conferred resistance to M. marinum infection. Sterol depletion with methyl-beta-cyclodextrin phenocopies the absence of vacuolins and confers resistance to infection. We have evidence that ESAT-6, the pore-forming toxin common to M. tuberculosis and M. marinum, is less associated with membranes when vacuolins were absent. Together, these results suggest that vacuolins and sterol-rich membrane microdomains are important host factors that are manipulated by mycobacteria to inflict membrane damage, escape from their compartment and efficiently proliferate in their host.
