Animal Models Core

动物模型核心

• 批准号: 10089395
• 负责人: Randall J Basaraba
• 金额: $ 32.43万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089395
• 关键词: Aerosols; Animal Model; Animals; Bacteria; Biological Markers; Cause of Death; Cavia; Cessation of life; Clinical; Cohort Studies; Colorado; Diagnosis; Diet; Disease; Disease Progression; Drug resistance; Drug resistance in tuberculosis; Gene Mutation; Human; Human Resources; Individual; Infection; Insulin Resistance; Laboratories; Lung; Medical; Metabolic; Metabolism; Modeling; Multi-Drug Resistance; Mycobacterium tuberculosis; Non-Insulin-Dependent Diabetes Mellitus; Patients; Pharmaceutical Preparations; Pharmacotherapy; Predisposition; Pulmonary Tuberculosis; Resistance; Risk Factors; The Sun; Therapeutic; Tuberculosis; Universities; antimicrobial drug; burden of illness; comorbidity; design; disorder control; experience; improved; in vivo; metabolomics; multidisciplinary; novel strategies; pathogen; porcine model; resistant strain; response

The Animal Models Core (D) is located within the Mycobacteriology Laboratory on the campus of Colorado State University. The Animal Infection Core is multidisciplinary with the expertise, personnel and facilities to model Mtb infection in guinea pigs with drug susceptible and resistant human clinical isolates as well as laboratory Mtb strains with targeted gene mutations. Our laboratory is also experienced and well equipped to model Mtb infection in guinea pigs with concurrent non-communicable diseases that are known TB risk factors in humans. Relevant to this proposal, we have developed the first ever model of Mtb infection in guinea pigs with diet-induced insulin resistance and type 2 diabetes that accurately mimics the comorbidity of tuberculosis and emerging noncommunicable diseases. In addition, we have designed and validated novel strategies to quantify pulmonary and extra-pulmonary tuberculosis disease burden in guinea pigs in response to experimental aerosol infection with drug susceptible and multi-drug resistant strains of Mycobacterium tuberculosis. We have recently characterized the profound alterations in systemic and cellular metabolism in response to Mycobacterium tuberculosis infection alone and demonstrated how preexisting alterations in host metabolism influences host susceptibility and in vivo disease progression. The Animal Models Core will parallel human cohort studies to 1) identify host metabolic determinants of tuberculosis disease control and progression and 2) use metabolomics to discover bacterial determinates of drug resistance and the discovery of host- and pathogen-derived biomarkers for tuberculosis diagnosis. Using the guinea pig model to study altered host metabolism associated with Mycobacterium tuberculosis infection has not only improved our understanding of the host-pathogen interaction but has identified potentially important therapeutic strategies that can be used as adjunct therapy in combination with conventional antimicrobial drug therapy. To fully exploit this model, the substantial existing core capabilities will be expanded to discover and validate additional biomarkers of altered host metabolism in guinea pigs infected with drug susceptible and drug resistant Mycobacterium tuberculosis.

动物模型核心（D）位于科罗拉多校园的分枝杆菌学实验室内 州立大学。动物感染核心是多学科的专业知识，人员和设施， 用药物敏感和耐药人临床分离株在豚鼠中建立Mtb感染模型，以及 实验室Mtb菌株的靶向基因突变。我们的实验室经验丰富，设备齐全， 患有已知结核病风险的并发非传染性疾病的豚鼠模型Mtb感染 人类的因素。与此相关的是，我们在2011年开发了第一个结核病感染模型。 具有饮食诱导的胰岛素抵抗和2型糖尿病的豚鼠，其准确地模拟了共患病 结核病和新出现的非传染性疾病。此外，我们设计并验证了新颖的 量化豚鼠肺结核和肺外结核疾病负担的策略 对药物敏感和多重耐药菌株的实验性气溶胶感染的反应 结核分枝杆菌。我们最近描述了系统和 细胞代谢的结核分枝杆菌感染，并证明了如何 宿主代谢的预先存在的改变影响宿主易感性和体内疾病进展。的 动物模型核心将平行于人类队列研究，以1）确定宿主代谢决定因素， 结核病的控制和进展，2）使用代谢组学来发现结核病的细菌决定因素， 耐药性以及发现用于结核病诊断的宿主和病原体衍生的生物标志物。 利用豚鼠模型研究结核分枝杆菌相关的宿主代谢改变 感染不仅提高了我们对宿主-病原体相互作用的理解， 潜在重要的治疗策略，可用作辅助治疗， 常规抗菌药物治疗。为了充分利用这一模式，现有的大量核心能力 将扩展到发现和验证豚鼠宿主代谢改变的其他生物标志物 感染药物敏感和耐药结核分枝杆菌。