Structural and biophysical characterization of the interaction between intracellular pathogens and phagosome membranes

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Bacteria can be ingested by professional phagocytes. Within the phagosome different mechanisms lead to a killing of the bacteria. However, some bacterial species are able to survive within the phagosome. The interaction between these intracellular bacteria and phagosome membranes is a key to understand how the pathogens survive in this niche. Besides proteins, lipids play an essential role in this process. However, up to now only limited data on the lipid composition and the physicochemical membrane properties are published. We want to characterize the lipidome of sub-cellular compartments and compare them depending on the absence or presence of bacteria which arrest phagosome maturation at a pre-phagolysosome stage. Based on these results, we will investigate the underlying molecular mechanisms of survival using biophysical approaches. For this, we will analyze purified phagosome membranes as well as reconstituted lipid membranes composed of well defined lipid compositions mimicking the phagosome membrane. In particular the interactions of the glycolipid trehalose-dimycolate (TDM) from Mycobacteria and of the virulence-associated protein A (VapA) from Rhodococcus equi will be characterized in detail using these systems.