Talk by Fikadu G. Tafesse
Title: "The roles of lipids in bacterial and viral infection"
Occasion: SFB Special Seminar
Host: Joost Holthuis
Start: 19.09.2022 - 16:15
Location: CellNanOs 38/201
About the speaker: Dr. Fikadu Tafisse is Associate Professor of Molecular Microbiology and Immunology, Department of Medicine at Oregon Health & Science University Portland, USA.
Abstract of the talk: Despite the continuous effort to end the spread of infectious diseases, they remain the leading cause of death worldwide. Our laboratory studies host-pathogen interactions of viruses (SARS-CoV-2, Zika virus and HIV) and bacteria (M. tuberculosis). We are especially interested in studying the role of cellular lipids in microbial pathogenesis and their significance on innate and adaptive immunity. In this seminar, I will discuss our finding that M. tuberculosis, the causative agent of tuberculosis, uses the sphingomyelin biosynthesis pathway to enter phagocytic cells to establish infection. I will also discuss our recent studies on how emerging and re-emerging pathogens remodel the host lipidome during infection. Using non-targeted lipidomics, we mapped alterations in host lipids following Zika virus and SARS-CoV-2 infections. ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Remarkably, SARS-CoV-2 also rewires host lipid metabolism, significantly altering hundreds of lipid species during infection. We correlate these changes with viral protein activity by transfecting human cells with each SARS-CoV-2 protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that small-molecule glycerolipid biosynthesis inhibitors can block SARS-CoV-2 propagation. This inhibition was effective against the different SARS-CoV-2 variants of concern, indicating that glycerolipid biosynthesis is a conserved host dependency factor supporting this evolving virus.