Advancing Analytical Methods for Investigating the Epidemiology of Antimicrobial Resistance using Campylobacter coli from Swine Populations as a Model System

使用猪群中的弯曲杆菌作为模型系统，改进研究抗菌素耐药性流行病学的分析方法

• 批准号: 10453455
• 负责人: Christine Anne Wang
• 金额: $ 4.64万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453455
• 关键词: Animal Feed; Animals; Antibiotics; Antimicrobial Resistance; Automobile Driving; Biological Models; Campylobacter coli; Campylobacter infection; Clinical; Communicable Diseases; Computational Biology; Computing Methodologies; Data; Development; Disease Management; Drug usage; Ecology; Economics; Environment; Epidemiologic Methods; Epidemiologist; Epidemiology; Evolution; Excision; Factor Analysis; Family suidae; Farm; Future; Genotype; Goals; Graph; Health; Human; Infection; Infectious Disease Epidemiology; Interdisciplinary Study; Investigation; Knowledge; Livestock; Longevity; Macrolide-resistance; Macrolides; Medical; Mentorship; Methods; Mission; Modeling; Molecular; Molecular Computations; Molecular Epidemiology; Mutation; North Carolina; Outcomes Research; Pharmaceutical Preparations; Phenotype; Physicians; Population; Population Genetics; Prevention strategy; Process; Production; Public Health; Research; Research Training; Resistance; Resources; Risk; Risk Factors; Sampling; Science; Scientist; Series; System; Time; Training; Translating; United States National Institutes of Health; Universities; Work; Zoonoses; advanced analytics; analytical method; antimicrobial; antimicrobial resistant pathogen; bacterial fitness; burden of illness; clinically significant; cohort; comparative; cost; epidemiology study; experience; experimental study; fitness; fluoroquinolone resistance; genetic approach; improved; insight; knowledge base; microbial; novel; pathogen; pressure; resistance mutation; skills; whole genome

PROJECT SUMMARY/ABSTRACT The emergence and persistence of antimicrobial resistant pathogens are a serious threat to human and animal populations worldwide. Although antimicrobial use is known to select for antimicrobial resistance (AMR), resistance often persists in the absence of antimicrobial exposure. An improved understanding of the epidemiology of AMR in natural pathogen populations is needed. However, traditional epidemiological methods are not well-suited for understanding AMR risk factors because they do not account for the ecological and evolutionary processes that confound the expected association between antimicrobial exposure and AMR. Improved epidemiological methods that incorporate ecological and evolutionary principles are necessary for providing new insights on AMR, informing more effective AMR prevention strategies, and ultimately promoting the future efficacy of antimicrobial therapies. The long-term goal of this research is to develop a quantitative framework integrating ecological and evolutionary principles with epidemiological methods to advance existing knowledge of AMR risk among human and animal populations. This proposal aims to use commensal Campylobacter coli populations in commercial swine herds as a model system to investigate the ecology, evolution, and epidemiology of AMR. Prior studies found that C. coli from pigs reared under both conventional and antibiotic-free farms were resistant to fluoroquinolone and macrolide antibiotics, which is clinically significant as these drugs are used to treat human campylobacteriosis. The proposed research will build upon this previous work and accomplish the following aims: 1) identify and quantify host exposures and microbial genotypes associated with phenotypic resistance to fluoroquinolone and macrolide drugs among commensal C. coli in swine herds using probabilistic graphical models (i.e. chain graphs), and 2) quantify selection and bacterial fitness costs of genotypes associated with fluoroquinolone- and macrolide-resistance among natural C. coli populations in presence and absence of antimicrobial use, using phylodynamic methods. The expected outcome of this research is the development of a quantitative framework that can be applied to any host-pathogen system in which AMR is a threat to elucidate drivers of AMR selection and persistence. This proposal and mentorship team will provide training critical for the applicant’s development as an independent clinician-scientist studying infectious disease epidemiology at the human-animal interface. The interdisciplinary research training plan will provide the applicant opportunities to develop skills in molecular epidemiology, computational biology and infectious disease epidemiology. The comparative clinical training plan will enable the applicant to gain experience in infectious disease management among both human and animal populations under the guidance of infectious disease physicians and veterinary epidemiologists. The training environment at North Carolina State University is ideal for the applicants cross-disciplinary training goals, as the applicant also has access to resources and opportunities at Duke University and University of North Carolina-Chapel Hill.

项目概要/摘要 抗菌药物耐药病原体的出现和持续存在对人类和动物构成严重威胁 全世界的人口。尽管众所周知，抗菌药物的使用会导致抗菌药物耐药性 (AMR)， 在没有接触抗菌药物的情况下，耐药性常常持续存在。加深了对 需要对自然病原体群体中的 AMR 进行流行病学研究。然而，传统的流行病学方法 不太适合理解 AMR 风险因素，因为它们没有考虑到生态和 进化过程混淆了抗菌药物暴露与抗菌素耐药性之间的预期关联。 需要改进结合生态学和进化原理的流行病学方法 提供有关 AMR 的新见解，为更有效的 AMR 预防策略提供信息，并最终促进 抗菌疗法的未来疗效。本研究的长期目标是开发一种定量的 将生态和进化原理与流行病学方法相结合的框架，以推进现有的 了解人类和动物群体中的 AMR 风险。该提案旨在利用共生 商业猪群中的大肠杆菌群体作为研究生态学的模型系统， AMR 的演变和流行病学。先前的研究发现，在两种传统方法下饲养的猪中都存在大肠杆菌。 无抗生素农场对氟喹诺酮类和大环内酯类抗生素产生耐药性，这具有临床意义 因为这些药物用于治疗人类弯曲菌病。拟议的研究将建立在先前的研究基础上 工作并实现以下目标：1) 识别和量化宿主暴露和微生物基因型 与猪共生大肠杆菌对氟喹诺酮类和大环内酯类药物的表型耐药性相关 使用概率图形模型（即链图）进行畜群分析，2) 量化选择和细菌适应性 自然大肠杆菌群体中与氟喹诺酮类和大环内酯类耐药性相关的基因型成本 在存在或不存在抗菌药物使用的情况下，使用系统动力学方法。本次活动的预期结果 研究是开发一个定量框架，可应用于任何宿主-病原体系统 AMR 是一种威胁，旨在阐明 AMR 选择和持续存在的驱动因素。这个提案和指导团队 将为申请人作为独立临床医生科学家的发展提供至关重要的培训 人与动物界面的传染病流行病学。跨学科研究培训计划将 为申请人提供发展分子流行病学、计算生物学和 传染病流行病学。比较临床培训计划将使申请人获得 指导下的人类和动物种群传染病管理经验 传染病医生和兽医流行病学家。北卡罗来纳州立大学的训练环境 大学是申请人实现跨学科培训目标的理想选择，因为申请人还可以获得 杜克大学和北卡罗来纳大学教堂山分校的资源和机会。