Metabolism of phytate and inositol by Legionella and implications for bacterial virulence

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The environmental bacterium Legionella pneumophila causes a severe pneumonia termed “Legionnaires’ disease”. L. pneumophila is a facultative intracellular pathogen that grows in nutrient broth, as well as in free-living amoebae and macrophages in the lung. Amino acids are regarded the prime carbon and energy source of L. pneumophila. However, the genome sequence, transcriptome data and metabolism studies indicate that L. pneumophila possess broad metabolic capacities and also utilizes carbohydrates. To replicate intracellularly, L. pneumophila secretes into host cells “effector proteins” that target phosphoinositide (PI) lipids. A translocated PI phosphatase is structurally related to phytases (myo-inositol hexakisphosphate phosphatases), raising the possibility that a dual function enzyme directly links metabolism and virulence of L. pneumophila. In this application, we propose to analyze (i) extra- and intracellular growth of L. pneumophila on phytate and inositol as a source of phosphorus, carbon and/or energy, respectively, (ii) phytase activity and secretion of an L. pneumophila PI phosphatase, (iii) L. pneumophila mutant strains lacking genes involved in phytate or inositol metabolism, (iv) subcellular compartmentalization of phytate or inositol metabolism in infected amoebae, and (v) the isotopologue profiles of [13C]phytate and [13C]inositol degradation by L. pneumophila.