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

军团菌对植酸和肌醇的代谢及其对细菌毒力的影响

• 批准号: 201136674
• 负责人: Professor Dr. Hubert Hilbi
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/201136674?language=en
• 关键词: Metabolism; phytate; inositol; Legionella; implications

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.

环境细菌嗜肺军团菌可引起一种被称为“军团病”的严重肺炎。嗜肺性乳杆菌是一种兼性细胞内病原体，它生长在营养肉汤中，也生长在肺中自由生活的阿米巴和巨噬细胞中。氨基酸被认为是嗜肺乳杆菌的主要碳源和能源。然而，基因组序列、转录组数据和代谢研究表明，嗜肺乳杆菌具有广泛的代谢能力，也利用碳水化合物。为了在细胞内复制，嗜肺性乳杆菌向宿主细胞分泌以磷脂酰肌醇(PI)为目标的“效应蛋白”。一个转位的PI磷酸酶在结构上与植酸酶(肌醇六糖磷酸酶)相关，这增加了一种双功能酶直接连接嗜肺链球菌新陈代谢和毒力的可能性。在这一应用中，我们建议分析(I)嗜肺乳杆菌在植酸盐和肌醇作为磷、碳和/或能量来源的胞外和胞内生长，(Ii)嗜肺乳杆菌的植酸酶活性和分泌，(Iii)嗜肺乳杆菌突变株缺乏涉及植酸或肌醇代谢的基因，(Iv)受感染的阿米巴中植酸或肌醇代谢的亚细胞区划，以及(V)嗜肺乳杆菌降解[13C]植酸和[13C]肌醇的同位素图谱。