Project 2: Defining multiscale dynamics of strains, genes and resistance in bacterial pathogens

项目 2：定义细菌病原体菌株、基因和抗性的多尺度动力学

• 批准号: 10610395
• 负责人: Ashlee Miriam Earl
• 金额: $ 72.95万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-10 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10610395
• 关键词: Project; Defining; multiscale; dynamics; strains

Project Summary Bacterial diseases kill millions of people worldwide each year, despite the advent of antibiotics 90 years ago. Emergence and spread of new and rapidly evolving pathogens with increased virulence, resistance to antibiotics, and transmissibility is increasingly straining efforts to manage infections and save lives. To combat this trend, we need a comprehensive and systematic understanding of the complex dynamics between the host, including host microbiota, and pathogen at every level of interaction—cellular, individual, and population levels. Our proposed studies leverage recent advances in sequencing technologies, innovative high-throughput molecular and multi-omic approaches, access to unique patient cohorts, and novel computational methods to characterize the genomes, transcriptomes, and individual strain-level interactions of bacterial pathogens with their hosts and other microbiota. In collaboration with renowned infectious disease researchers, clinicians, and epidemiologists, we will target critical gaps in our understanding of key infectious disease threats—uropathogenic Escherichia coli (UPEC), carbapenem resistant Enterobacteriaceae (CRE), and multidrug resistant enterococci. Specifically, we will i) ​determine the gut-to-urinary tract dynamics of UPEC in recurrent urinary tract infections; ii) track the multiscale dynamics of antibiotic resistance gene proliferation - from individual microbiota to local and global circulation; and iii) characterize the dynamic functional reservoir of MDR enterococci. While our aims focus on ESKAPE pathogens, our goal is to pioneer and disseminate a comprehensive technological framework and resources to empower clinical and research communities working to understand, diagnose, prevent, and treat infectious diseases.

项目概要 尽管出现了抗生素，但细菌性疾病每年仍导致全世界数百万人死亡 90年前。新的和快速进化的病原体的出现和传播 毒力、抗生素耐药性和传播性正日益加大努力的难度 控制感染并拯救生命。为了应对这一趋势，我们需要全面、 系统地了解宿主之间的复杂动态，包括宿主微生物群， 和病原体在各个相互作用水平上——细胞、个体和群体水平。我们的 拟议的研究利用了测序技术的最新进展，创新 高通量分子和多组学方法，获得独特的患者队列，以及 表征基因组、转录组和个体的新颖计算方法 细菌病原体与其宿主和其他微生物群的菌株水平相互作用。在 我们与著名的传染病研究人员、临床医生和流行病学家合作， 将针对我们对主要传染病威胁——尿路致病性的理解中的关键差距 大肠杆菌 (UPEC)、耐碳青霉烯类肠杆菌 (CRE) 和多药 耐药肠球菌。具体来说，我们将 i)​确定 UPEC 的肠道到泌尿道动力学 复发性尿路感染； ii) 追踪抗生素耐药性的多尺度动态 基因增殖——从个体微生物群到局部和全球循环； iii) 表征 耐多药肠球菌的动态功能库。虽然我们的目标集中在 ESKAPE 病原体，我们的目标是开创和传播一个全面的技术框架 和资源，使临床和研究社区能够理解、诊断、 预防、治疗传染病。