Metabolic adaptation drives pathogenicity of C. difficile epidemic strain RT078

项目概要/摘要 艰难梭菌是抗生素相关性腹泻的最常见原因，已成为抗生素相关性腹泻的最常见原因之一。 美国和欧洲最常见的医院感染。 In the early 2000’s, there was a world-wide 艰难梭菌感染（CDI）爆发，疾病严重程度增加。 RT078 strains emerged as 2003 年流行菌株，是医院中最常见的分离菌株之一。 Several studies have RTo78 菌株与 RT027 一起被描述为艰难梭菌最常见的核糖型之一 recent outbreaks;然而，患病率和疾病严重程度增加的原因仍然不清楚 明白了。有趣的是，RT078 是在家畜中发现的最丰富的核糖型，包含一个新的 4 基因 我们假设代谢操纵子促进人畜共患传播。该提案旨在研究饮食作为 使艰难梭菌从动物传播到人类的人畜共患病的重要因素。 The overall objectives of 该提案旨在评估最近添加到人类饮食中的多糖代谢对 临床分离 RT078 菌株的竞争适应性和疾病严重程度，并了解其中的原因 核糖体型在世界各地的农场动物中占据主导地位。了解临床意义 C. 艰难梭菌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为医院提供 CDI 爆发期间患者的饮食指南。

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.