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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.

摘要痢疾每年影响世界上数以亿计的人，其特征是肠道组织和血管破裂，因此可见数量的血液在排便过程中丢失。痢疾可由病毒、细菌或寄生虫感染引起。肠道病原体福氏志贺氏菌是细菌性痢疾的病原体，导致2.5亿以上的痢疾病例每年造成20多万人死亡。抗击细菌性痢疾的一个主要挑战是缺乏一种小动物模型，它概括了在感染个体中观察到的症状。我们的团队已经最近发现，与人类相似，感染福氏志贺氏菌的幼兔经历了严重的免疫细胞渗出，结肠粘膜大量溃烂，血性腹泻。在此应用程序中，我们建议通过(1)细菌特性探讨福氏杆菌野生型和突变型幼兔模型的建立负担和相关的组织病理学(Aim1)和宿主基因表达谱的特征(Aim 2)。本申请中提出的幼兔模型的特征将提供关键的分子工具以了解支持人类细菌性痢疾的机制。