Epidemiology and Genomics of Clostridium difficile

艰难梭菌的流行病学和基因组学

• 批准号: 8026742
• 负责人: David M Aronoff
• 金额: $ 39.15万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-02 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8026742
• 关键词: Acute; Adult; Affect; Anaerobic Bacteria; Antibiotics; Bacteria; Behavior; Biological; Cessation of life; Clinical; Clostridium difficile; Colitis; Collection; Community-Acquired Infections; Cytotoxin; Data; Diagnosis; Diagnostic; Diarrhea; Discrimination; Disease; Elderly; Epidemic; Epidemiology; Figs - dietary; Foundations; Genetic; Genetic Determinism; Genetic Variation; Genomics; Goals; Healthcare; Hospitals; Human; Incidence; Individual; Infection; Intestines; Methods; Modeling; Molecular; Morbidity - disease rate; Outcome; Pathogenesis; Patients; Phylogenetic Analysis; Population Genetics; Prevention; Preventive; Public Health; Recurrence; Refractory Disease; Regimen; Relapse; Resources; Risk Assessment; Severities; Single Nucleotide Polymorphism; Specimen; System; Testing; Therapeutic; Toxin; base; clinically relevant; comparative; experience; genetic analysis; genome sequencing; global health; high throughput screening; innovation; microbial; microbial host; mortality; pathogen; patient population; tool

Clostridium difficile is a toxin-producing bacterium that is a frequent cause of hospital-acquired and antibiotic-associated diarrhea. The incidence and severity of C. difficile infection (CDI) are increasing, in parallel with increases in community-acquired infections, making CDI a major public health problem. Following inoculation, patients may clear C. difficile from their intestinal tract, become asymptomatically colonized, or develop CDI, ranging in severity from mild diarrhea to fulminant colitis and/or death. Older adults are disproportionately affected by CDI, experiencing greater morbidity and mortality. Antibiotics treat CDI, but refractory disease and relapses occur. Major gaps exist in our understanding ofthe host and microbial factors that determine the outcome of human contact with C. difficile. The broad objective of this ERIN CRC is to develop innovative approaches to the diagnosis, prevention, and treatment of CDI based on understanding the molecular mechanisms of disease. The goals of this Proiect are to use genomic information obtained from clinical C. difficile strains, to identify microbial determinants of infection and develop a rapid, high-throughput assay to predict the clinical behavior of individual C. difficile strains. We hypothesize that there is a genomic basis for the different clinical presentations of C. difficile (colonization, mild or severe infection, and relapse) in susceptible hosts. The Specific Aims of this proposal seek to: (1) Establish a collection of isolates that spans the genetic diversity of C. difficile associated with both asymptomatically colonized adults and those with initial and recurrent infection; (2) Perform a comparative phylogenomic analysis of representative C. difficile isolates obtained from Aim 1; and (3) Develop a high-throughput single nucleotide polymorphism (SNP) typing system for the rapid discrimination and risk-assessment ofC. difficile infection. This project will collect clinicoepidemiological data, biological specimens and C. difficile strains, which will be used in all three major projects of this ERIN.

艰难梭菌是一种产毒素细菌，是医院获得性和非感染性疾病的常见原因。 腹泻相关性腹泻。C.艰难梭菌感染（CDI）的增加，在社区获得性感染的增加，使CDI的一个主要的公共卫生问题。 接种后，患者可清除C。艰难梭菌从肠道排出，无症状地定植，或发展为CDI，严重程度从轻度腹泻到暴发性结肠炎和/或死亡。老年人受CDI的影响不成比例，发病率和死亡率更高。抗生素治疗CDI，但难治性疾病和复发发生。我们对决定人类与C.很难ERIN CRC的广泛目标是在了解疾病分子机制的基础上，开发诊断、预防和治疗CDI的创新方法。本项目的目标是利用临床上获得的C.艰难梭菌菌株，以确定感染的微生物决定因素，并开发一种快速，高通量的测定来预测个体C.艰难菌株我们推测，有一个基因组的基础上，不同的临床表现的C。艰难梭菌（定植，轻度或重度感染，复发）在易感宿主。具体目标是 建议：（1）建立一个跨越C.艰难 与无症状定殖的成年人以及初始和复发感染的人相关;（2）对代表性的C.（3）建立一种高通量的单核苷酸多态性（SNP）分型系统，用于C.艰难感染本项目将收集临床流行病学资料、生物学标本和C.艰难梭菌菌株，这将用于该ERIN的所有三个主要项目。