Effector glycosyltransferases of the human pathogen Legionella pneumophila

• Applicant: Professor Dr. Klaus Aktories
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Pharmacology ; Cell Biology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233993717

Legionella pneumophila is a human pathogen, which causes severe pneumonia called Legionnaires disease. The bacterium invades and replicates inside alveolar macrophages. Therefore, Legionella injects effector proteins by type-IV-secretion into the host cytosol to arrange an intracellular Legionella-containing vacuole (LCV) where Legionella can replicate. The Legionella effectors SetA and Lpg1961 show high sequence similarities to glycosyltransferases and are toxic when introduced into eukaryotic cells. SetA was implicated in the subversion of eukaryotic vesicle trafficking. The function of Lpg1961 is unknown. Initial biochemical studies showed that SetA possesses an N-terminal glycosyltransferase domain and a C-terminal PtdIns(3)P-binding domain. Using yeast genetics, cell biology and protein biochemical methods, the host substrates of the glycosyltransferases should be identified and the molecular and functional consequences of their glycosylation elucidated. We aim to analyze the structure-function relationships of glycosyltransferases SetA and Lpg1961. The proposed studies should clarify the effects of the glycosyltransferases in the host cells and their roles during the Legionella infection process.

• DFG Programme: Research Grants
• Participating Person: Dr. Thomas Jank