Interactions of alpha-proteobacteria with eukaryotic cells

我们研究计划的长期目标是了解α-蛋白细菌和真核细胞之间相互作用的分子基础。这类细菌包括动物和人类病原体(巴尔通氏菌、布鲁氏菌、Ochrobactrum)、植物病原菌(农杆菌)和植物共生菌(中生根瘤菌、根瘤菌、中华根瘤菌)以及自由生活的细菌。近年来，许多α-蛋白细菌的基因组序列变得可用。基于这些丰富的信息，旨在了解这类细菌不同生存策略的后基因组研究现在是可能的。我们选择Ochrobactrum属作为我们的研究项目，因为它的不同物种反映了从自由生活的土壤细菌到植物共生体和条件人类病原体的广泛生活方式。在下一个资助期，我们工作的主要模型将是机会致病菌人间变态杆菌。这种细菌生活在土壤中，但从医院免疫抑制患者中分离出这种细菌的报告数量一直在增加，这表明它具有显著的致病潜力。由于对人类的致病性不大，可以在生物安全级别2的条件下进行研究，这是我们长期研究计划的重要先决条件。在下一个资助期，我们将研究人间棘球菌胞内转运及其毒力基因的调控。这项工作将为一种全面的系统方法奠定基础，该方法将使用与细胞内生长过程中调节的基因的融合来表征病原体的代谢反应。在我们长期研究计划的背景下，我们将把我们的研究扩展到Ochrobactrum属植物的共生和自由生活成员。这一分析将为不同的生存策略提供有趣的新见解，这些策略使密切相关的细菌能够生活在非常不同的环境中。

The long-term objective of our research program is to understand the molecular basis of the interactions between alpha-proteobacteria and eukaryotic cells. This group of bacteria comprises animal and human pathogens (Bartonella, Brucella, Ochrobactrum), plant pathogens (Agrobacterium) and plant symbionts (Mesorhizobium, Rhizobium, Sinorhizobium) as well as free-living bacteria. The genomic sequences of many alpha-proteobacteria became available in recent years. Based on this wealth of information, post-genomic studies are now possible that are aimed at understanding the different survival strategies of this group of bacteria. We have chosen the genus Ochrobactrum for our research program as its different species reflect a broad spectrum of life styles from free-living soil bacteria to plant symbionts and opportunistic human pathogens. The principal model for our work during the next funding period will be the opportunistic pathogen Ochrobactrum anthropi. This organism lives in soil, but the number of reports on its isolation from immuno-suppressed patients in hospitals has been increasing, suggesting that it has significant pathogenic potential. As the pathogenicity for humans is modest, O. anthropi can be studied under biosafety level 2 conditions, which is an important pre-requisite for our long-term research plans. In the next funding period, we will characterize the intracellular trafficking of O. anthropi and the regulation of its virulence genes. This work will set the stage for a comprehensive systems approach, which will use fusions to genes regulated during intracellular growth to characterize the metabolic responses of the pathogen. In the context of our long-term research program we will extend our research to plant symbiotic and free-living members of the genus Ochrobactrum. This analysis will provide fascinating novel insights into the different survival strategies that enable closely related bacteria to live in very different environments.