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首页> 外文期刊>Applied Microbiology >Metabolism of myo-Inositol by Legionella pneumophila Promotes Infection of Amoebae and Macrophages
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Metabolism of myo-Inositol by Legionella pneumophila Promotes Infection of Amoebae and Macrophages

机译：嗜肺军团菌对肌醇的代谢促进变形虫和巨噬细胞的感染。

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Legionella pneumophila is a natural parasite of environmental amoebae and the causative agent of a severe pneumonia termed Legionnaires' disease. The facultative intracellular pathogen employs a bipartite metabolism, where the amino acid serine serves as the major energy supply, while glycerol and glucose are mainly utilized for anabolic processes. The L. pneumophila genome harbors the cluster lpg1653 to lpg1649 putatively involved in the metabolism of the abundant carbohydrate myo -inositol (here termed inositol). To assess inositol metabolism by L. pneumophila , we constructed defined mutant strains lacking lpg1653 or lpg1652 , which are predicted to encode the inositol transporter IolT or the inositol-2-dehydrogenase IolG, respectively. The mutant strains were not impaired for growth in complex or defined minimal media, and inositol did not promote extracellular growth. However, upon coinfection of Acanthamoeba castellanii , the mutants were outcompeted by the parental strain, indicating that the intracellular inositol metabolism confers a fitness advantage to the pathogen. Indeed, inositol added to L. pneumophila -infected amoebae or macrophages promoted intracellular growth of the parental strain, but not of the Δ iolT or Δ iolG mutant, and growth stimulation by inositol was restored by complementation of the mutant strains. The expression of the P_( iol ) promoter and bacterial uptake of inositol required the alternative sigma factor RpoS, a key virulence regulator of L. pneumophila . Finally, the parental strain and Δ iolG mutant bacteria but not the Δ iolT mutant strain accumulated [U-~(14)C_(6)]inositol, indicating that IolT indeed functions as an inositol transporter. Taken together, intracellular L. pneumophila metabolizes inositol through the iol gene products, thus promoting the growth and virulence of the pathogen.IMPORTANCE The environmental bacterium Legionella pneumophila is the causative agent of a severe pneumonia termed Legionnaires' disease. The opportunistic pathogen replicates in protozoan and mammalian phagocytes in a unique vacuole. Amino acids are thought to represent the prime source of carbon and energy for L. pneumophila . However, genome, transcriptome, and proteome studies indicate that the pathogen not only utilizes amino acids as carbon sources but possesses broader metabolic capacities. In this study, we analyzed the metabolism of inositol by extra- and intracellularly growing L. pneumophila . By using genetic, biochemical, and cell biological approaches, we found that L. pneumophila accumulates and metabolizes inositol through the iol gene products, thus promoting the intracellular growth, virulence, and fitness of the pathogen. Our study significantly contributes to an understanding of the intracellular niche of a human pathogen.
机译：嗜肺军团菌是环境变形虫的天然寄生虫，是被称为军团菌病的严重肺炎的病原体。兼性细胞内病原体利用双部分代谢，其中氨基酸丝氨酸为主要能量供应，而甘油和葡萄糖主要用于合成代谢过程。嗜肺乳杆菌基因组具有簇lpg1653至lpg1649，推测其参与了丰富的碳水化合物肌醇（此处称为肌醇）的代谢。为了评估肺炎链球菌的肌醇代谢，我们构建了缺少lpg1653或lpg1652的已定义突变菌株，这些菌株分别编码肌醇转运蛋白IolT或肌醇-2-脱氢酶IolG。突变菌株在复杂的或限定的基本培养基中生长不受影响，并且肌醇不促进细胞外生长。然而，在同时感染棘阿米巴棘孢菌后，突变体被亲代菌株竞争，表明细胞内肌醇代谢赋予该病原体适当的优势。实际上，添加到肺炎链球菌感染的变形虫或巨噬细胞中的肌醇促进了亲本菌株的细胞内生长，但没有促进ΔiolT或ΔiolG突变体的细胞内生长，并且通过突变体菌株的互补来恢复肌醇的生长刺激。 P_（iol）启动子的表达和肌醇的细菌摄取需要替代性的sigma因子RpoS，它是肺炎链球菌的关键毒力调节剂。最后，亲本菌株和ΔiolG突变细菌积累了[U-〜（14）C_（6）]肌醇，但没有ΔiolT突变菌株积累，表明IolT确实起肌醇转运蛋白的作用。总之，细胞内肺炎支原体通过iol基因产物代谢肌醇，从而促进病原体的生长和毒力。重要提示肺炎军团菌是一种严重的肺炎病原体，被称为军团菌病。机会病原体在独特的液泡中在原生动物和哺乳动物的吞噬细胞中复制。氨基酸被认为是肺炎支原体的主要碳和能量来源。但是，基因组，转录组和蛋白质组学研究表明，病原体不仅利用氨基酸作为碳源，而且具有更广泛的代谢能力。在这项研究中，我们分析了细胞外和细胞内生长的嗜肺乳杆菌的肌醇代谢。通过使用遗传，生化和细胞生物学方法，我们发现肺炎链球菌通过iol基因产物积累并代谢肌醇，从而促进了病原体的细胞内生长，毒力和适应性。我们的研究为理解人类病原体的细胞内生态位做出了重要贡献。

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