Strategies of Bacteroides fragilis to acquire iron in the intestinal tract.

项目摘要/摘要： 共生类杆菌属(Colteroids spp.)约占人类结肠细菌总数的30%-40%。这 环境是一个竞争激烈的生态系统，对于拟杆菌属来说。来维持他们的高细胞 数量，他们需要有效地竞争可用的营养物质，如铁与其他微生物 微生物区系。营养铁对肠道微生物区系有显著影响。对铁的竞争 通过共生改变共生微生物区系和铁的觅食保护免受 病原体和结肠炎。这支持了类杆菌属的一种作用。在肠道铁稳态中。然而， 类杆菌利用的铁获取机制。在复杂的微生物中争夺铁 人类结肠的生态系统还没有被研究过。在本申请中，我们展示了脆弱类杆菌 利用其他生物产生的铁结合铁载体(异铁载体)在铁下生长 厌氧性的极限条件。此外，我们还鉴定了一种依赖于TonB的外膜转运蛋白 只存在于脆弱芽孢杆菌BfFchA1中，参与利用铁结合的铁载体在 厌氧条件。此外，我们还提出铁是从铁铁载体上解离/还原出来的。 周质空间中的复合体，因为铁的内化依赖于跨膜 铁质运输系统FeoAB。因此，这些研究将扩大我们对脆弱芽孢杆菌铁的理解。 动态平衡及其对肠道定植的贡献。对于此应用程序，我们的假设是BfFchA1 和FeoAB对脆弱芽孢杆菌肠道定植过程中铁的获取起关键作用。为了检验我们的假设，我们将在 目标1)确定BfFchA1在铁载体厌氧同化中的作用，并在目标2)确定 BfFchA1和FeoAB在脆弱芽孢杆菌肠道定植小鼠模型中的作用。这些研究的长期目标是 是提供靶点，可能导致开发新的益生菌治疗策略 鉴于脆弱杆菌有益的免疫调节特性，预防或治疗肠道疾病。

Project Summary/Abstract: The commensal Bacteroides spp. account for about 30-40% of total bacteria in the human colon. This environment is a highly competitive ecosystem and in order for Bacteroides spp. to maintain their high cell number, they need to compete efficiently for the available nutrients such as iron with other microorganisms of the microflora. Nutritional iron has a remarkable influence on the gut microflora. The competition for iron changes the commensal microflora and iron foraging by commensals protect against colonization by pathogens and colitis. This supports a role for Bacteroides spp. in intestinal iron homeostasis. However, the iron acquisition mechanisms utilized by Bacteroides spp. to compete for iron in the complex microbial ecosystem of the human colon have not been examined. In this application we show that Bacteroides fragilis utilize ferric iron-bound siderophores produced by other organisms (xenosiderophores) to grow under iron limiting conditions anaerobically. In addition, we have identified a TonB-dependent outer membrane transporter present only in B. fragilis, BfFchA1, involved in the utilization of ferric iron-bound siderophore for growth under anaerobic conditions. Moreover, we propose that iron is dissociated/reduced from the ferric iron-siderophore complex in the periplasmic space because the internalization of iron is dependent on the transmembrane ferrous iron transporter system FeoAB. Thus, these studies will expand our understanding of B. fragilis iron homeostasis and its contribution to intestinal colonization. For this application, our hypothesis is that BfFchA1 and FeoAB are critical for B. fragilis iron acquisition during gut colonization. To test our hypothesis, we will in aim 1) define the role of BfFchA1 in ferri-siderophore assimilation anaerobically and in aim 2) define the role of BfFchA1 and FeoAB in B. fragilis intestinal colonization in a mouse model. The long term goal of these studies is to provide targets that could lead to the development of new probiotic therapeutic strategies for the prevention or treatment of intestinal disorders in view of B. fragilis beneficial immunomodulatory properties.