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Sie sind hier: Startseite Funded Projects Antje Flieger (2011-2017)

Antje Flieger (2011-2017)

Significance of Legionella pneumophila phospholipases for modification of lipids within the phagosomal membrane

Legionellae are intracellular pathogens and the causative agent of Legionnaires disease, a potentially fatal pneumonia. Phospholipases may contribute to bacterial virulence, for example via modification of eukaryotic membranes. At least 18 phospholipases, including three GDSL phospholipases A / sterol acyltransferases, have been described for L. pneumophila. Most of these activities are delivered into the host cell via type IVB (Dot/Icm) secretion, type II (Lsp) secretion, or by means of outer membrane vesicles and consequently get in contact with the phagosomal membrane. It has been described that dramatic changes occur at the Legionella-containing phagosomal membrane which is transformed into an endoplasmic reticulum-like compartment within minutes after Legionella infection. However, the lipid composition of this compartment and whether phospholipases contribute to the lipid rearrangements is currently not known. Most interestingly within the first project period, a specific change in the proteins associated with wild type versus GDSL triple mutant phagosomes was observed. One protein, whose mammalian homologue is involved in eicosanoid generation, was only present in wild type phagosomes. Eicosanoids are important lipid mediators and we showed that L. pneumophila indeed induces their production. In the here described second project period, the impact of the L. pneumophila phospholipases on the lipid composition of the Legionella-containing vacuole will be investigated focussing on the three GDSL enzymes PlaA, PlaC, and PlaD. Additionally, the role of bacterial factors, especially phospholipases A, for eicosanoid generation and the function of the eicosanoid synthesis proteins localized at the phagosome will be analysed.