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.

艰难梭菌是一种产生毒素的细菌，是医院获得性和感染性肺炎的常见原因。 抗生素相关性腹泻。艰难梭菌感染 (CDI) 的发病率和严重程度不断增加，同时社区获得性感染也在增加，这使得 CDI 成为一个主要的公共卫生问题。 接种后，患者可能会从肠道中清除艰难梭菌，成为无症状定植，或出现 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 的影响尤为严重，发病率和死亡率更高。抗生素可以治疗 CDI，但难治性疾病和复发也会发生。我们对决定人类接触艰难梭菌结果的宿主和微生物因素的理解存在重大差距。 ERIN CRC 的总体目标是在了解疾病的分子机制的基础上开发诊断、预防和治疗 CDI 的创新方法。该项目的目标是利用从临床艰难梭菌菌株获得的基因组信息，识别感染的微生物决定因素，并开发一种快速、高通量的检测方法来预测个别艰难梭菌菌株的临床行为。我们假设易感宿主中艰难梭菌的不同临床表现（定植、轻度或重度感染以及复发）存在基因组基础。本次活动的具体目标 该提案旨在：(1) 建立涵盖艰难梭菌遗传多样性的分离株集合 与无症状定植成人以及初次和复发感染的成人相关； (2) 对从目标 1 获得的代表性艰难梭菌分离株进行比较系统发育分析； （3）开发高通量单核苷酸多态性（SNP）分型系统，用于快速鉴别和风险评估C.艰难梭菌感染。该项目将收集临床流行病学数据、生物标本和艰难梭菌菌株，这些数据将用于本次ERIN的全部三个主要项目。