Characterization of an infant rabbit model of bacillary dysentery

幼兔细菌性痢疾模型的表征

基本信息

批准号：
10203818
负责人：
HERVE F AGAISSE
金额：
$ 19.71万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10203818
关键词：
Actins Address Adult Affect Age Animal Model Animals Antibiotic Therapy Antimicrobial Resistance Bacteria Bacterial Infections Blood Blood Vessels Cavia Cells Cellular biology Cessation of life Child Colon Cytoskeleton Cytosol Defecation Development Disease Disease Outcome Dose Dysentery Endothelial Cells Epithelial Cells Eye Feces Fibroblasts Foundations Gene Expression Genes Hemorrhagic colitis Histopathology Hour Human Human Volunteers Immune Immune response In Situ Hybridization In Vitro Individual Infant Infection Infiltration Intestinal Mucosa Intestines Invaded Knowledge Lesion Lung Maps Modeling Molecular Morbidity - disease rate Mucous Membrane Mus Oral Oryctolagus cuniculus Outcome Parasitic infection Pathogenesis Pathologic Patients Property Route Rupture Seminal Shigella Infections Shigella flexneri Site Small Intestines Symptoms System Therapeutic Intervention Tissue-Specific Gene Expression Tissues Tumor-infiltrating immune cells Type III Secretion System Pathway Ulcer Virus Diseases Work base cell motility cell type design diarrheal disease enteric pathogen experience experimental study macrophage mortality mutant neutrophil nonhuman primate pathogen pathogenic bacteria preventive intervention response tissue culture tool transcriptome sequencing

项目摘要

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.

抽象的痢疾每年影响世界上数亿人，其特征是损害肠道组织和血管破裂，因此可见的血液随着排便而失去。痢疾可能是由病毒，细菌或寄生虫感染引起的。肠道病原体志贺氏菌Flexneri是细菌痢疾的病因，并负责超过2.5亿个痢疾病例每年，导致超过200,000人死亡。打击细菌痢疾的主要挑战是缺乏一个小动物模型，该模型概括了感染个体中观察到的症状。我们的小组有最近发现，与人类类似的婴儿，感染了链球菌的婴儿兔子经历了严重的免疫细胞浸润，结肠粘膜的大规模溃疡和血腥的腹泻。在此应用程序中，我们建议通过（1）细菌的表征探索具有野生型和突变体S. flexneri的婴儿兔模型负担和相关的组织病理学（AIM1）和宿主基因表达谱的表征（AIM 2）。本应用中提出的婴儿兔模型的表征将提供关键的分子工具理解支持人类细菌痢疾的机制。