Clostridium difficile Cooperative Research Center

艰难梭菌合作研究中心

• 批准号: 8508834
• 负责人: VINCENT B YOUNG
• 金额: $ 138.76万
• 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/8508834
• 关键词: Address; Adult; Antibiotic-Associated Colitis; Antibiotics; Area; Bacteria; Bioinformatics; Biological Markers; Biology; Blood; Characteristics; Clinical; Clinical Medicine; Clostridium difficile; Collection; Communicable Diseases; Dendritic Cells; Development; Discrimination; Disease; Disease susceptibility; Eating; Ecology; Emerging Communicable Diseases; Enteral; Epidemiology; Epigenetic Process; Evolution; Feces; Frequencies; Gastrointestinal tract structure; Genetic Determinism; Genomics; Genotype; Geriatrics; Germ; Germination; Goals; Health; Human; Human Genetics; Immune response; Immunology; Indigenous; Individual; Infection; Inpatients; Knowledge; Laboratories; Lead; Mediating; Medical; Michigan; Modality; Modeling; Molecular; Molecular Epidemiology; Morbidity - disease rate; Mus; Outcome; Outpatients; Paper; Pathogenesis; Pathway interactions; Patients; Pilot Projects; Play; Positioning Attribute; Predisposition; Process; Production; Prospective Studies; Recurrence; Regulation; Regulatory T-Lymphocyte; Reproduction spores; Research; Research Activity; Research Infrastructure; Research Personnel; Resistance; Risk Assessment; Role; Sampling; Scheme; Series; Serum; Severities; Single Nucleotide Polymorphism; Specimen; Staging; Surveys; System; Testing; Therapeutic Uses; Toxin; United States National Institutes of Health; Universities; Variant; Virulence; clinical infrastructure; cytokine; disease phenotype; enteric pathogen; follow-up; gut microbiota; human DNA; human subject; interest; microbial; mortality; multidisciplinary; mutant; neutrophil; novel; novel diagnostics; novel therapeutics; pathogen; prevent; programs; public health relevance; rapid diagnosis; research study; response

DESCRIPTION (provided by applicant): The University of Michigan Enterics Research Investigational Network Cooperative Research Center (UM ERIN CRC) is composed of an integrated, multidisciplinary team of investigators who have expertise in bacterial pathogenesis, microbial ecology, immunology, human genetics, infectious diseases, bioinformatics, clinical medicine and geriatrics. To leverage the expertise of the assembled team, their current research interests and past research accomplishments, the UM ERIN CRC will focus its efforts on the study of antibiotic-associated colitis due to Clostridium difficile. C. difficile infection (CDI) is a re-emerging infectious disease that is responsible for significant morbidity and mortality. However, despite the significance of CDI, there are major gaps in our knowledge of the pathogenesis of this infection. To address these gaps, the UM ERIN CRC will carry out three projects. In the first project a clinical survey will be conducted to collect clinical specimens (feces, blood and human DNA) and C. difficile strains from asymptomatically infected individuals and patients with initial episodes or recurrent CDI of varying severity. The C. difficile strains will be genetically characterized to understand the role of bacterial diversity/evolution in the disease process. This information will be used to develop a rapid single-nucleotide polymorphism typing scheme to aid in rapid diagnosis and molecular epidemiology. The second project will utilize the clinical specimens and clinical strains to determine the role of the indigenous microbiota in CDI. Specific hypotheses regarding gut microbial ecology and CDI will be tested in a novel murine model that we have activated in our laboratory group. The last portion of this project involves examination of the relationship between the ability of C. difficile to sporulate/germ in ate and the pathogenesis of CDI. The spore biology of the clinical strains from the first project will be characterized and variants tested for the ability to persist and cause disease using the murine model. Targeted mutants of the sporulation pathway will also be constructed and characterized. The third project will leverage the clinical specimens and the murine model of CDI to characterize the role of the host response in CDI pathogenesis. The role of innate and adaptive immune responses in mediating clinical disease and susceptibility will be determined by examining responses and biomarkers in samples from human clinical cases and the murine model. These integrated projects will increase our understanding of C. difficile disease and lead to novel diagnostic and therapeutic modalities for this increasingly important pathogen.

描述(由申请人提供)：密歇根大学肠道研究调查网络合作研究中心(UM Erin CRC)由一个综合的、多学科的研究团队组成，他们拥有细菌发病机制、微生物生态学、免疫学、人类遗传学、传染病、生物信息学、临床医学和老年学方面的专业知识。为了利用聚集的团队的专业知识、他们目前的研究兴趣和过去的研究成就，UM Erin CRC将把重点放在艰难梭菌引起的抗生素相关性结肠炎的研究上。艰难梭菌感染(CDI)是一种新出现的传染病，导致严重的发病率和死亡率。然而，尽管CDI很重要，但我们对这种感染的发病机制仍有很大的认识空白。为弥补这些差距，UM Erin儿童基金会将实施三个项目。在第一个项目中，将进行临床调查，收集临床标本(粪便、血液和人类DNA)和艰难梭菌菌株，这些标本来自无症状感染者和具有不同严重程度的首发或复发CDI的患者。艰难梭菌菌株将进行基因特征分析，以了解细菌多样性/进化在疾病过程中的作用。这些信息将被用来开发快速单核苷酸多态分型方案，以帮助快速诊断和分子流行病学。第二个项目将利用临床标本和临床菌株来确定本土微生物区系在CDI中的作用。关于肠道微生物生态学和CDI的特定假设将在我们实验室小组激活的一个新的小鼠模型中进行测试。该项目的最后部分涉及艰难梭菌在ATE中产孢子/芽胞的能力与CDI发病机制之间的关系的检查。第一个项目的临床菌株的孢子生物学将被表征，并使用小鼠模型测试变种的持久性和致病能力。还将构建产孢子途径的靶向突变体并对其进行鉴定。第三个项目将利用临床标本和CDI的小鼠模型来表征宿主反应在CDI发病机制中的作用。先天和获得性免疫反应在调节临床疾病和易感性方面的作用将通过检测人类临床病例和小鼠模型样本中的反应和生物标记物来确定。这些综合项目将增加我们对艰难梭菌疾病的了解，并为这种日益重要的病原体带来新的诊断和治疗方式。