The intracellular metabolism of Legionella pneumophila and its regulation

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Legionella pneumophila (Lp) is commonly found in freshwater habitats and acts as the agent of Legionnaires´ disease. Although various virulence factors of Lp have been reported, less is known about intracellular nutrition and metabolism in adaptation of the host cell. We have shown by isotopologue profiling that amino acids (e.g. serine) as well as glucose serve as a major carbon source for Lp grown in culture to synthesize amino acids and PHB. In contrast to the general view, we could demonstrate that glucose is metabolized via the Entner-Doudoroff (ED) pathway and that the ED pathway is necessary for full in vivo virulence of Lp. Lp secretes an eukaryotic-like glucoamylase GamA to degrade glycogen and starch. Notably, GamA is active during intracellular replication in amoebae highlighting the role of carbohydrate nutrition under intracellular conditions. On the basis of these results, we will now analyse the in vivo metabolism of Lp using different hosts. The study is aimed to identify and to quantify the metabolite fluxes in adaptation of the various host conditions. To this end, isotopologue and metabolite profiling will be used comparing in vitro data for all organisms under study with those from in vivo experiments. The analysis will also include the less virulent species L. oakridgensis as well as mutant strains of Lp lacking known regulators or key enzymes for intracellular metabolism. The understanding of the metabolic strategies of different Legionella species will lead to a better understanding of fitness, virulence and persistence of legionellae and may lead to better methods for fighting these pathogens.