The influence of glutamine transporters and global regulators on metabolism, colonization and virulence of Streptococcus pneumoniae

谷氨酰胺转运蛋白和全局调节因子对肺炎链球菌代谢、定植和毒力的影响

• 批准号: 71820458
• 负责人: Professor Dr. Sven Hammerschmidt
• 金额: --
• 依托单位: Abteilung Molekulare Genetik und Infektionsbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/71820458?language=en
• 关键词: influence; glutamine; transporters; global; regulators

Streptococcus pneumoniae (pneumococci) are versatile human pathogenic bacteria. Besides viru-lence factors, the maintenance of pneumococcal fitness during adaptation to different host milieus is also of central importance in causing local infections and invasive pneumococcal diseases (IPD) in humans. The regulation of amino acid uptake systems including glutamine transporters or sugar uptake systems is likely crucial for the fitness of pneumococci in the nasopharynx or during IPD. As bacterial fitness and virulence are tightly linked we will investigate the role of metabolic regula-tors such as ArgR, GlnR, or Rex, of the enzymes of the arginine deiminase system (ADS), and of the enzyme Zwf for pneumococcal fitness and virulence. Mice infection experiments and phagocy-tosis studies using macrophages and pneumococcal mutants deficient for the transcriptional regu-lators, ADS, and Zwf will be conducted to assess the impact of these bacterial factors on S. pneumoniae virulence and intracellular survival. The individual role of the regulators or metabol-ic enzymes on pneumococcal metabolism will be studied by applying isotopolomics and metabo-lomics. We will further decipher and compare the metabolism between pneumococci cultured un-der in vitro conditions in a synthetic medium and under in vivo conditions, i.e. when pneumococci were taken up by macrophages. This will be done by analysing the isotopologue profiles and moni-toring the extracellular and intracellular bacterial metabolites of phagocytosed pneumococci.

肺炎链球菌（肺炎球菌）是一种多用途的人类致病菌。除了毒力因素外，在适应不同宿主环境的过程中维持肺炎球菌的适应性对于引起人类局部感染和侵袭性肺炎球菌疾病（IPD）也至关重要。氨基酸摄取系统（包括谷氨酰胺转运体或糖摄取系统）的调节可能对肺炎球菌在鼻咽部或IPD期间的适应性至关重要。由于细菌适应性和毒力紧密相关，我们将研究代谢调节剂如ArgR、GlnR或Rex、精氨酸脱亚胺酶系统（ADS）酶和Zwf酶在肺炎球菌适应性和毒力中的作用。利用巨噬细胞和缺乏转录调节因子ADS和Zwf的肺炎球菌突变体进行小鼠感染实验和吞噬研究，以评估这些细菌因子对肺炎链球菌毒力和细胞内存活的影响。将应用同位素组学和代谢组学研究调节因子或代谢酶在肺炎球菌代谢中的个体作用。我们将进一步破译和比较体外条件下在合成培养基中培养的肺炎球菌和体内条件下（即肺炎球菌被巨噬细胞吞噬时）的代谢。这将通过分析同位素剖面和监测吞噬肺炎球菌的细胞外和细胞内细菌代谢物来完成。