Characterization of an infant rabbit model of bacillary dysentery

摘要 痢疾每年影响世界上数亿人，其特征是损害 肠组织和血管破裂，因此可见数量的血液随着排便而流失。 痢疾可以由病毒、细菌或寄生虫感染引起。肠道病原体福氏志贺菌是 是细菌性痢疾的病原体，造成了2.5亿多例痢疾病例 每年造成20多万人死亡。防治细菌性痢疾的一个主要挑战是缺乏 一个小动物模型，重现了在感染个体中观察到的症状。我们集团 最近发现，与人类相似，感染S.弗氏经历了严重的免疫 细胞浸润、结肠粘膜大面积溃疡和血性腹泻。在本申请中，我们提出 探讨野生型和突变型S.通过（1）细菌的表征 负荷和相关组织病理学（Aim 1）以及宿主基因表达谱表征（Aim 2）。 本申请中提出的幼兔模型的表征将提供关键的分子工具 以了解人类细菌性痢疾的发病机制。

Abstract Dysentery affects hundreds of millions of people in the world each year and is characterized by damage to the intestinal tissue and rupture of blood vessels, so that visible quantities of blood are lost with defecation. Dysentery can result from viral, bacterial, or parasitic infections. The intestinal pathogen Shigella flexneri is the causative agent of bacillary dysentery and is responsible for more than 250 million cases of dysentery annually, resulting in more than 200,000 deaths. A major challenge in combating bacillary dysentery is the lack of a small-animal model that recapitulates the symptoms observed in infected individuals. Our group has recently uncovered that similar to humans, infant rabbits infected with S. flexneri experienced severe immune cell infiltration, massive ulceration of the colonic mucosa, and bloody diarrhea. In this application, we propose to explore the infant rabbit model with wild type and mutant S. flexneri through (1) characterization of bacterial burden and associated histopathology (Aim1) and characterization of host gene expression profiles (Aim 2). The characterization of the infant rabbit model proposed in this application will provide critical molecular tools for understanding the mechanisms supporting bacillary dysentery in humans.