Rapid Emergence of Livestock-associated MRSA ST398: Host-adaptation & Virulence

牲畜相关 MRSA ST398 的快速出现：宿主适应

• 批准号: 8862356
• 负责人: Lance Bradley Price
• 金额: $ 38.73万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-10 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8862356
• 关键词: American; Animal Feed; Animal Model; Animals; Antibiotic Resistance; Asia; Back; Bacterial Antibiotic Resistance; Bacteriophages; Biological Assay; Case Study; Clinic; Collection; Communities; Country; Coupled; Denmark; Disease; Elements; Environment; Environmental Health; Epidemiologic Studies; Epidemiology; Europe; European; Evolution; Exhibits; Family suidae; Farming environment; Food; Frequencies; Future; Genes; Genetic Research; Genome; Genomics; Genotype; Geographic Distribution; Health; Household; Human; Immune; In Vitro; Individual; Infant; Infection; Infection Control; Intervention; Investigation; Iowa; Knowledge; Lead; Link; Livestock; Longitudinal Studies; Mediating; Microbial Genetics; Molecular; Netherlands; North America; Northern Europe; Phylogeny; Prevalence; Price; Production; Pseudogenes; Public Health; Qualifying; Relative (related person); Reporting; Research; Research Personnel; Resolution; Role; Route; Rural; Rural Health; Scientist; Sepsis; Skin Tissue; Soft Tissue Infections; Structure; Surveillance Program; Surveys; System; Techniques; Technology; Testing; Time; Translational Research; Virulence; Virulence Factors; assay development; base; cost effective; design; experience; farm worker; farmer; fitness; foodborne pathogen; gastrointestinal; genome sequencing; human disease; in vitro Model; innovation; killings; methicillin resistant Staphylococcus aureus; neutrophil; pathogen; public health intervention; repository; surveillance strategy; tool; transmission process

DESCRIPTION (provided by applicant): Since its discovery in 2004, livestock-associated MRSA ST398 has emerged as an increasingly common cause of human infections in Northern Europe and a prevalent colonizer of livestock and farm workers in the U.S. and around the world. A recent survey of Iowa hog farms showed that 70% of farms-and nearly half of the hog farmers-were positive for MRSA ST398. Meanwhile, the epidemiology of ST398 in Northern Europe appears to be shifting. Initially, all MRSA ST398 infections could be traced back to direct or indirect contact with livestock, but new cases without known livestock exposure are increasing, particularly in Denmark and the Netherlands. Yet, despite serious public health concerns, little is known about this rapidly emerging antibiotic-resistant pathogen. This is attributed in large part to the limitations of standard molecular analyses for elucidating the origins, evolution, and dispersal of the highly clonal ST398 lineage. To develop infection control and surveillance strategies, we must better understand the genomic changes that are facilitating the rapid emergence of MRSA ST398 and innovate more refined genotyping techniques to better characterize the reservoirs and transmission routes of human ST398 infection. In the current proposal, we will combine sequencing technologies with in vitro functional assays to assess the phylogenomic structure of ST398 (SA-1) and evaluate the genomic elements enabling human colonization and infection (SA-2, SA-3). We will further develop a set of high-resolution genotyping assays that can be applied in large- scale MRSA ST398 investigations (SA-4). To accomplish our proposed aims, we have assembled a highly qualified multi-national team: Dr. Price (PI; U.S.), an expert in environmental health, bacterial genomics, and translational research is uniquely qualified to lead this study; Dr. Keim (co-I; U.S.), a renowned expert in microbial genetics research will contribute to the genomics portion of this project, including the phylogenomics and assay development; Dr. Tara Smith (co-I; U.S.), a highly experienced American rural health researcher will conduct a longitudinal study of ST398 colonization and infection among U.S. farm workers; Drs. Robert Skov (co-I; Denmark) and Jan Kluytmans (co-I; the Netherlands), two clinician-scientists who have spearheaded the MRSA ST398 surveillance programs in their respective countries, will curate European ST398 isolate collections for the aims of this project. Key innovations of the current study include the application of phylogenomics to elucidate the MRSA ST398 sublineages and resolve the relative contribution of food-animal production on the emergence of this pathogen. Analyzing our unparalleled ST398 collections using a pan-genome approach will maximize our ability to discover genomic adaptations associated with human colonization and infection, as well as livestock-independent community dispersal. Successful completion of this project has the potential to immediately advance our understanding of an important antibiotic-resistant pathogen and facilitate our ability to mitigate its emergence.

描述（由申请人提供）：自2004年发现以来，与牲畜相关的MRSA ST398已成为北欧人类感染的日益普遍原因，以及美国和世界各地的牲畜和农场工人的普遍殖民者。最近对爱荷华州猪场的调查显示，MRSA ST398的农场中有70％的农场和近一半的猪农民。同时，北欧的ST398的流行病学似乎正在发生变化。最初，所有MRSA ST398感染都可以追溯到与牲畜的直接或间接接触，但是没有已知牲畜暴露的新病例正在增加，尤其是在丹麦和荷兰。然而，尽管有严重的公共卫生问题，但对这种快速出现的抗生素耐药性病原体知之甚少。这在很大程度上归因于标准分子分析的局限性，以阐明高度克隆ST398谱系的起源，进化和分散。为了制定感染控制和监视策略，我们必须更好地了解MRSA ST398快速出现的基因组变化，并创新了更精致的基因分型技术，以更好地表征人类ST398感染的储层和传播途径。在当前的建议中，我们将结合测序技术与体外功能测定法，以评估ST398（SA-1）的系统基因结构，并评估实现人类定植和感染的基因组元素（SA-2，SA-3）。我们将进一步开发一组高分辨率的基因分型测定，可大规模应用MRSA ST398研究（SA-4）。为了实现我们的拟议目标，我们组建了一支高素质的跨国团队：Price博士（PI; U.S.），环境健康，细菌基因组学和翻译研究专家，具有独特的资格来领导这项研究；著名的微生物遗传学研究专家Keim（Co-I; U.S.）将为该项目的基因组学部分做出贡献，包括系统基因组学和测定开发；一位经验丰富的美国农村健康研究人员Tara Smith博士（Co-I; U.S.）将对美国农场工人的ST398殖民和感染进行纵向研究；博士。罗伯特·斯科夫（Co-i;丹麦）和扬·克鲁伊特曼（Jan Kluytmans）（Co-I;荷兰）是两位临床医生，他们在其各自的国家率先进行了MRSA ST398监视计划，将策划欧洲ST398 ST398 is alter筹集该项目的目标。当前研究的关键创新包括应用系统基因学阐明MRSA ST398 sublineages，并解决食品 - 动物产生对该病原体出现的相对贡献。使用泛基因组方法分析我们无与伦比的ST398收集，将最大程度地发现我们发现与人类定植和感染相关的基因组适应以及与牲畜无关的社区分散的能力。该项目的成功完成有可能立即提高我们对重要抗生素病原体的理解，并促进我们减轻其出现的能力。