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

项目概要/摘要： 细菌类杆菌属（Bacteroides spp.）约占人体结肠中细菌总数的30-40%。这 环境是一个高度竞争的生态系统，为了使拟杆菌。以维持他们的高细胞 数量，它们需要有效地与其他微生物竞争可用的营养素，如铁。 微生物群落营养铁对肠道菌群有显著影响。铁的竞争 通过改变微生物区系和铁的觅食， 病原体和结肠炎。这支持拟杆菌属的作用。在肠道铁平衡中的作用但 拟杆菌属利用的铁获取机制在复杂的微生物中竞争铁 人类结肠的生态系统尚未被研究。在本申请中，我们表明脆弱拟杆菌 利用其他生物产生的铁结合铁载体（异铁载体）在铁下生长 限制条件厌氧。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B中。fragilis，BfFchA 1，参与利用三价铁结合的铁载体在 厌氧条件此外，我们提出铁是从三价铁载体解离/还原的， 复合物在周质空间，因为铁的内化是依赖于跨膜 亚铁转运蛋白系统FeoAB。因此，这些研究将扩大我们对B的理解。脆性铁 体内平衡及其对肠道定植的贡献。对于该应用，我们的假设是BfFchA 1 和FeoAB是B的关键。fragilis铁收购期间肠道定植。为了验证我们的假设，我们将在 目的1）定义BfFchA 1在厌氧铁-铁载体同化中的作用，以及目的2）定义 B中的BfFchA 1和FeoAB。fragilis肠道定植的小鼠模型。这些研究的长期目标是 是提供可能导致开发新的益生菌治疗策略的目标， 预防或治疗B方面的肠道疾病。fragilis有益的免疫调节特性。

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.