Analysis of export and membrane association of PlaB - a surface-associated phospholipase A and virulence factor of Legionella pneumophila

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Legionellae are intracellular pathogens and the causative agent of Legionnaires disease, a potentially fatal pneumonia. At least 18 different phospholipases including PlaB, a hemolytic phospholipase A, have been described for Legionella pneumophila. Recent analysis showed that PlaB-derived activity promotes virulence and is activated by a novel oligomer dissociation mechanism. Further, PlaB localizes to the bacterial surface although no signal peptide is predicted, the N-terminal region remains uncleaved, and the first 20 amino acids are not essential for export to the surface. Additionally, PlaB associates with membranes although no transmembrane domains, beta-barrel structures, typical signatures or modifications of lipoproteins have been found. This indicates that PlaB is not an integral but rather a peripheric membrane-associated protein and so far unknown interactions with membrane proteins or lipids accomplish membrane association. Since, none of the currently known secretion modes in L. pneumophila drives PlaB export to the surface, I hypothesize that a novel export mechanism is responsible for PlaB surface presentation. In the here presented project: 1) the L. pneumophila determinants and the regions within PlaB driving PlaB export to the surface, 2) interactors responsible for PlaB association with the membrane and respective PlaB regions involved, and 3) the contribution of the oligomeric state to export and membrane association will be analyzed.