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， 美国和欧洲最常见的医院感染。在2000年代初，有一个世界范围的 艰难梭菌感染（CDI）爆发，疾病严重程度增加。RT 078菌株出现为 是2003年的流行菌株，是医院中最常见的分离菌株之一。几项研究 将RTo 78菌株与RT 027一起沿着鉴定为C.艰难期间 最近的疫情;然而，流行率和疾病严重程度增加的原因仍然不清楚 明白有趣的是，RT 078是在家畜中发现的最丰富的核糖体型，并且含有新的4基因 代谢操纵子，我们假设促进人畜共患病转移。这项提案旨在研究饮食作为一种 重要因素，使人畜共患转移的C。从动物到人类都很难。的总体目标 这项建议是为了评估最近加入到人类饮食中的多糖的代谢对 临床分离的RT 078菌株的竞争适应性和疾病严重程度，并了解为什么这 核糖体基因型在世界范围内的家畜中占主导地位。了解临床意义C. difficile谱系利用饮食营养来源的变化，以及这些适应如何影响 这些菌株的传播可以告知医院在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.