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Characterization of virulence factors in shigellosis

志贺氏菌病毒力因子的表征

基本信息

批准号：
10724770
负责人：
HERVE F AGAISSE
金额：
$ 25.38万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10724770
关键词：
Actins Address Agreement Animal Model Animals Bacteria Blood Blood Vessels Cells Cessation of life Collaborations Colon Complex Cytoskeleton Cytosol Data Development Disease Dysentery Epithelial Cells Epithelium Feces Genes Grant Hemorrhagic colitis Histology Hour Human Immune Immune system In Vitro Individual Infant Infection Inflammation Intestinal Mucosa Invaded Investigation Lamina Propria Lesion Location Membrane Modeling Mucous Membrane Oryctolagus cuniculus Outcome Pathogenesis Phase Phenotype Plasmids Process Proteins Role Seminal Shigella Infections Shigella flexneri Survival Rate Symptoms System Techniques Testing Type III Secretion System Pathway Ulcer Vacuole Virulence Virulence Factors bacterial fitness cell motility cell type diarrheal disease enteric pathogen experience experimental study fitness immune cell infiltrate in vivo intestinal epithelium mutant nonhuman primate pathogen success tissue culture transposon sequencing uptake

项目摘要

Abstract The intestinal pathogen Shigella flexneri is the causative agent of bacillary dysentery (bloody diarrhea) 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 has been the lack of a small-animal model that recapitulates the symptoms observed in infected individuals. Our group has recently developed a unique model of bacillary dysentery in infant rabbits. In this model, animals infected with S. flexneri experience massive epithelial cell fenestration, vascular lesions, immune cell infiltration, and bloody diarrhea. While the bacterial factors supporting S. flexneri intracellular infection have been chiefly determined using tissue culture systems, we know very little about the virulence determinants leading to pathogenesis in infected individuals. In this application, we propose to use the infant rabbit model in conjunction with Transposon-sequencing approaches to identify and characterize the bacterial factors supporting bacillary dysentery.

摘要肠道病原体福氏志贺菌是细菌性痢疾（血性腹泻）的病原体，每年造成2.5亿多起痢疾病例，造成20多万人死亡。一对抗细菌性痢疾的一个主要挑战是缺乏一个小动物模型，在感染者身上观察到的症状。我们的团队最近开发了一种独特的细菌模型，幼兔痢疾在该模型中，感染S.弗氏体经历大量上皮细胞穿孔、血管病变、免疫细胞浸润和血性腹泻。而细菌因素支持S.福氏菌胞内感染主要是用组织培养系统确定的，对导致感染个体发病的毒力决定因素知之甚少。在这应用，我们建议使用婴儿兔模型结合转座子测序方法鉴定和表征支持细菌性痢疾的细菌因子。