Metabolic cross-talk between Bartonella henselae and host cells

汉赛巴尔通体与宿主细胞之间的代谢串扰

• 批准号: 71697933
• 负责人: Professor Dr. Volkhard A. J. Kempf
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie und Krankenhaushygiene
• 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 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/71697933?language=en
• 关键词: Metabolic; cross; talk; between; Bartonella

Slow growing humapathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders (bacillary angiomatosis). The facultative intracellular pathogen replicates rapidly within endothelial host cells suggesting that these cells represent an ecological niche supplying the bacterium with oxygen and nutrients. On the other hand, infections with B. henselae result in the activation of hypoxia-inducible factor (HIF)-1, the key transcription factor involved in host cell metabolism (glycolysis, oxygen supply via angiogenesis, and erythropoiesis). Preliminary experiments revealed that B. henselae do not replicate in endothelial cells with a HIF-1 knock-down. Additionally, we identified several B. henselae genes crucial for intracellular survival. Using cell culture models, we now want to analyze how the intracellular growth and persistence of the facultative intracellular pathogen B. henselae depends on HIF-1 activity. For this purpose, we have generated several HIF-1 knock down endothelial cell lines (using hairpin siRNA) and established methods for analyzing intracellular oxygen levels and HIF-1 activation pathways. Moreover, a novel Bartonella-liquid growth medium allows us to investigate which biological compounds (e.g. sucrose, amino acids) are required for the growth and persistence of B. henselae in host cells. The results of our investigations should (i) help to understand the metabolic cross-talk between intracellular bacteria (e.g. B. henselae) and their host cells on a molecular and cellular level and (ii) should possibly result in new therapeutic strategies for the treatment of infections with intracellular bacteria.

慢速生长的亨氏巴尔通氏杆菌可引起猫抓病和血管增生性疾病(细菌性血管瘤病)。这种兼性胞内病原体在内皮宿主细胞内迅速复制，表明这些细胞代表着为细菌提供氧气和营养的生态位。另一方面，感染亨氏假单胞菌导致低氧诱导因子(HIF)-1的激活，HIF-1是参与宿主细胞代谢(糖酵解、血管生成供氧和红细胞生成)的关键转录因子。初步实验表明，亨氏假单胞菌不能在HIF-1基因敲除的内皮细胞中复制。此外，我们还鉴定了几个对细胞内生存至关重要的亨塞氏杆菌基因。利用细胞培养模型，我们现在想要分析兼性细胞内病原体B.henselae的细胞内生长和持久性如何依赖于HIF-1活性。为此，我们已经建立了几个HIF-1击倒内皮细胞株(使用发夹siRNA)，并建立了分析细胞内氧水平和HIF-1激活途径的方法。此外，一种新型的巴尔通体液体培养基使我们能够研究哪些生物化合物(如蔗糖、氨基酸)是亨氏巴尔通体在宿主细胞中生长和持续存在所必需的。我们的研究结果应该有助于(I)在分子和细胞水平上了解细胞内细菌(如B.henselae)与其宿主细胞之间的代谢交互作用，以及(Ii)可能导致治疗细胞内细菌感染的新的治疗策略。