Long Polar Fimbriae of Attaching and Effacing Escherichia coli

附着和消除大肠杆菌(AEEC)毒力因子的表达受到严格调控 进程，在某些情况下，很难确定这些因素，因为它们要么 体外抑制或表达条件尚不清楚。虽然很明显，某些人的表达 毒力因子与人类疾病严格相关，AEEC菌株中存在的额外因子 与其致病过程有关的因素仍不清楚。缺乏对基因如何编码的充分了解 这些额外的毒力因素得到控制是重要的，因为如果没有这些知识，我们不太可能 了解AEEC菌株的整体致病特性。因此，我们的目标是确定 AEEC菌株中的长极(LP)菌毛与致病有关，并利用这些菌毛编码基因 作为检测强毒菌株的标记。中心假设是，除了已经表征的 定植因素(例如，内膜介导的黏附)，AEEC菌株具有高度调节的LP菌毛， 这在定居过程中发挥了作用，尽管编码这些菌毛的基因广泛存在 一些Lp菌毛类型分布在致病性大肠杆菌菌株中，仅在特定的AEEC菌株中发现。 我们将通过三个具体的目标来检验这一假设：1)定义LER和H-NS是否充当 选择性沉默/反沉默防御系统控制AEEC菌株中LP菌毛的表达；2) 非典型肺上皮细胞Lp菌毛表达调控蛋白S的鉴定及在兔体内的检测 模拟Lp菌毛在定殖过程中的作用；以及3)描述Lp菌毛的分布 AEEC菌株之间的基因簇，并确定某些LP菌毛亚基类型是否可靠 不同致病性AEEC菌株的标记。为了实现我们的目标，我们将充分描述这些功能 体外和活体条件下LER、H-NS和非典型肠源性大肠杆菌编码调节子(幼兔)的研究 定植模型)条件，并对LPF基因在特定亚群中的流行率进行详细研究 致病性AEEC菌株。我们的研究工作具有创新性，因为它利用了我们在以下方面的发现 AEEC菌株中新的定植因子及其在治疗和诊断中的潜在应用。这个 控制LP菌毛表达的调控网络的研究结果具有重要意义，因为 我们将能够找出根本的差异来解释不同AEEC菌株的组织趋向性，并 确定Lp菌毛沉默是否是AEEC菌株防御系统的一个例子 水平获得的基因。此外，兔子模型的使用将使我们对 AEEC菌株的致病机制和定植特性。对潜在机制的理解 AEEC在胃肠道的定植不仅将进一步加深我们对这些疾病发病机制的了解 但也为降低感染率和改善治疗方案提供了机会 这些生物制剂被归类为B类病原体，因为它们可能对食品安全构成威胁。

The expression of Attaching and Effacing Escherichia coli (AEEC) virulence factors is a tightly regulated process, and, in some cases, the identification of these factors has been difficult because they are either repressed in vitro or the conditions of expression are unknown. While it is evident that expression of certain virulence factors is strictly associated with human disease, the additional factors present in AEEC strains that are linked to their pathogenic process remain unclear. Lack of a full understanding of how the genes encoding these additional virulence factors are controlled is important, because, without this knowledge, we are unlikely to understand the overall pathogenic properties of AEEC strains. Thus, our objective is to determine how the Long Polar (LP) fimbriae in AEEC strains contribute to pathogenesis and to use these fimbrial-encoding genes as markers to detect virulent strains. The central hypothesis is that, in addition to the already characterized colonization factors (e.g., intimin-mediated adhesion), AEEC strains possess a highly regulated LP fimbriae, that plays a role in the colonization process, and although the genes encoding these fimbriae are widely distributed in pathogenic E. coli strains, some LP fimbriae types are found exclusively in specific AEEC strains. We will test this hypothesis through three specific aims, which are to: 1) Define whether Ler and H-NS act as a selective silencing/anti-silencing defense system that controls LP fimbriae expression in AEEC strains; 2) Identify the regulatory protein(s) controlling LP fimbriae expression in atypical EPEC and determine in a rabbit model the function of LP fimbriae during colonization; and 3) Characterize the distribution of the LP fimbrial gene clusters among AEEC strains and determine whether certain LP fimbrial subunit types are reliable markers of different pathogenic AEEC strains. To accomplish our aims, we will fully characterize the functions of Ler, H-NS, and atypical enteropathogenic E. coli-encoded regulators under in vitro and in vivo (infant rabbit colonization model) conditions and perform a detailed study of prevalence of the lpf genes in specific subsets of pathogenic AEEC strains. Our research work is innovative because it capitalizes on our findings regarding novel colonization factors in AEEC strains and their potential application in therapeutics and diagnostics. The results from studies of the regulatory networks controlling LP fimbriae expression have significance, because we will be able to identify fundamental differences to explain the tissue tropism of different AEEC strains and to determine whether silencing of LP fimbriae is an example of a defense system that AEEC strains have against horizontally acquired genes. In addition, the use of the rabbit model will give us new insight into the pathogenesis and colonization properties of AEEC strains. An understanding of the mechanisms underlying AEEC colonization to the gastrointestinal tract will not only further our knowledge of the pathogenesis of these organisms but also provide opportunities for reducing infection rates and improving treatment options against these biological agents classified as category B pathogens due to their potential use as a food safety threat.