Priority Research Area Infections

Host-Microbe Interactome

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Mission

Lipid Dynamics during Mycobacterial Infections

Header_Raw macrophages infected with M. marinum. ©Barisch.

Tuberculosis (Tb) is caused by Mycobacterium tuberculosis and remains one of the deadliest infectious diseases. The World Health Organization (WHO) estimates that in 2021, Tb killed 1.6 million people emphasizing the importance to develop new drugs, vaccines and diagnostic tools to reduce this burden in the future.

M. tuberculosis employs multiple strategies to survive intracellularly. One of its most striking adaptations is its ability to utilize host lipids such as fatty acids and sterols to: (i) generate energy, (ii) build its characteristic lipid-rich cell wall and (iii) produce storage lipids during infection. To be constantly in a fatty acid-rich environment, the pathogen actively contributes to generate the “foamy” phenotype in host macrophages, for which the accumulation of host lipid droplets (LDs) is characteristic.

Using the Dictyostelium discoideum/M. marinum infection system, we found that mycobacteria access host LDs to build up their own lipid storage organelles and exploit ER-derived phospholipids when LDs are lacking (Barisch et al., 2015; Barisch & Soldati, 2017). Moreover, we observed that mycobacteria that escaped from the Mycobacterium-containing vacuole (MCV) into the cytosol recruit LD-derived enzymes and regulatory proteins on their hydrophobic surface.

Left: Dgat2-GFP-labelled LDs interact with cytosolic mycobacteria (from Barisch and Soldati, 2017).
Right: LD interaction with cytosolic mycobacteria leads to the re-distribution of LD proteins on the mycobacterial surface (from Barisch and Soldati, 2017).

Key Interests

The Barisch lab aims to unravel the molecular mechanisms by which pathogenic mycobacteria acquire lipids from their host to support chronic infection. Combining the application of functionalized lipid probes with mass spectrometry-based lipidomics and advanced microscopy techniques, the group analyses metabolic lipid flows between mycobacteria and their host at the subcellular and ultrastructural level.

More information: www.barischlabcssb.com