Metabolic adaptation drives pathogenicity of C. difficile epidemic strain RT078

代谢适应驱动艰难梭菌流行菌株 RT078 的致病性

基本信息

批准号：
10226948
负责人：
Heather A. Danhof
金额：
$ 5.25万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-04-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10226948
关键词：
Animal Feed Animals Avena sativa Biological Assay Bioreactors Body Weight decreased Carbohydrates Carbon Catabolism Cecum Centers for Disease Control and Prevention (U.S.)Clinical Clostridium difficile Colon Communities Complement Complex Data Diet Dietary Polysaccharide Dietary Sugars Disaccharides Disease Disease Outbreaks Enzymes Epidemic Epidemiology Europe Feces Gene Cluster Genes Genetic Genome Growth Histopathology Hospitals Human Infection Inulin Label Link Livestock Measures Metabolic Metabolism Monitor Nosocomial Infections Nutrient Operon Pathogenicity Patients Phosphotransferases Polysaccharides Population Prevalence Public Health Research Ribotypes Rice Severity of illness Signal Transduction Sorghum Source Starch Technology Testing Therapeutic Intervention Toxin Trehalose Virulence Wheat Work Zoonoses antibiotic-associated diarrhea arabinogalactan clinically significant dietary dietary guidelines dietary starch experimental study fitness fitness test genetic element human disease humanized mouse improved microbial community mouse model mutant novel sugar transmission process

项目摘要

Project Summary/Abstract Clostridium difficile is the most common cause of antibiotic associated diarrhea and has become one of the most frequent hospital acquired infections in the US and Europe. In the early 2000’s, there was a world-wide outbreak of Clostridium difficile Infection (CDI) with increased disease severity. RT078 strains emerged as epidemic strains in 2003 and are among the most commonly isolated strains in hospitals. Several studies have characterized RTo78 strains, along with RT027, as among the most prevalent ribotypes of C. difficile during recent outbreaks; however, the reason for increased prevalence and disease severity remains poorly understood. Interestingly RT078 are the most abundant ribotype found in livestock and contain a novel 4 gene metabolic operon that we hypothesize promotes zoonotic transfer. This proposal seeks to investigate diet as an important factor that enables zoonotic transfer of C. difficile from animals to humans. The overall objectives of this proposal are to assess the impact of metabolism of polysaccharides recently added to the human diet on the competitive fitness and disease severity of clinically isolated RT078 strains and to understand why this ribotype is so dominant in farm animals around the world. Understanding how clinically significant C. difficile lineages have utilized changes in dietary nutrient sources and how these adaptations impacts the transmission of these strains may inform hospitals on dietary guidelines for patients during CDI outbreaks.

项目摘要/摘要艰难梭菌是抗生素相关腹泻的最常见原因，已成为其中之一最常见的医院在美国和欧洲获得了感染。疾病严重程度增加的艰难梭菌感染（CDI）爆发。 2003年流行病，是医院中最常见的菌株之一。将RTO78菌株以及RT027的特征表征为艰难梭菌的最普遍的核糖型之一但是，最近的暴发；理解。我们假设的代谢操纵子促进了人畜共患病。将艰难梭菌从动物转移到人类的重要因素。该建议是评估最近人类饮食对多糖代谢的影响临床隔离的RT078菌株的竞争性适应性和疾病截止在世界各地的农场中，核糖型是如此。艰难的谱系在饮食中使用了改变的养分来源，以及策划如何影响在CDI暴发期间，菌株的传播可能会使患者降低。