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性腹泻的最常见原因，已成为 最常见的医院感染发生在美国和欧洲。2000年初，S在全世界范围内进行了一场 艰难梭菌感染(CDI)暴发，病情加重。RT078菌株出现了 2003年的流行菌株，是医院最常见的分离菌株之一。几项研究已经 将RTo78菌株与RT027一起鉴定为艰难梭菌最流行的核型之一 最近的暴发；然而，流行率和疾病严重性增加的原因仍然不充分 明白了。有趣的是，RT078是在家畜中发现的最丰富的核糖体类型，包含一个新的4基因 我们假设的代谢操纵子促进了人畜共患病的转移。这项提案寻求将饮食作为一种 使艰难梭菌能够从动物向人类进行人畜共患传播的重要因素。的总体目标 这项建议是为了评估最近添加到人类饮食中的多糖代谢对 临床分离的RT078菌株的竞争适合度和疾病严重性及其原因 核型在世界各地的农场动物中占主导地位。了解C.C.的临床意义 艰难梭菌的谱系利用了饮食营养来源的变化，以及这些适应如何影响 这些菌株的传播可能会向医院通报CDI暴发期间患者的饮食指南。