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

• 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
• 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

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。在2000年代初期，有一个全球 艰难梭菌感染（CDI）爆发，疾病严重程度增加。 RT078菌株出现为 2003年流行病，是医院中最常见的菌株之一。有几项研究 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 最近的爆发；但是，患病率增加和疾病严重程度的原因仍然很差 理解的是，RT078是牲畜中发现的最丰富的核糖型，并包含一个新颖的4基因 我们假设的代谢操纵子可以促进人畜共患病转移。该建议旨在调查饮食作为一种 将艰难梭菌从动物转移到人类的重要因素。总体目标 该建议旨在评估最近添加到人饮食中多糖代谢的影响 临床孤立的RT078菌株的竞争性适应性和疾病严重程度，并了解为什么 核糖型在世界各地的农场动物中是如此占主导地位。了解临床意义的C. 艰难的谱系利用了饮食中的营养来源的变化，这些适应如何影响 这些菌株的传播可能会在CDI暴发期间针对患者的饮食指南通知医院。