Antimicrobial Resistance Transmission Associated with Small-Scale Food-Animal Production in Peri-Urban Communities of Quito, Ecuador

项目总结/摘要 肠杆菌科细菌中抗菌素耐药性（AMR）流行率的增加已导致主要的临床 以及对人类医学的经济影响。发现许多多重耐药（MDR）肠杆菌科 是社区获得的，与食用动物（即为肉类和乳制品而饲养的牲畜）有关 产品）。本研究项目的目标是应用流行病学方法和下一代DNA 测序以定量E.大肠杆菌和移动的遗传元件（例如质粒， 转座子等）生活在厄瓜多尔基多东部城郊教区的食用动物和儿童之间的关系 小规模的食用动物生产非常普遍。这项研究将包括有年轻人的家庭。 三种社区类型的儿童：1）没有食用动物生产的社区; 2） 小规模的食用动物生产; 3）小规模和商业规模的食品- 动物生产。方法：在目标1中，我们将研究幼儿和食用动物是否共享E。杆菌 克隆[通过全基因组多位点序列分型（wgMLST）评估]， 表型多药耐药模式在目标2中，我们将确定MDR E。大肠杆菌菌株， 非克隆动物（通过wgMLST鉴定），但具有相同的表型多药耐药性 格局然后，我们将分析与观察到的表型抗性相关的移动的遗传元件 模式和表征的系统发育关系的移动的遗传因素负责 抗性基因转移在目标3a中，我们将研究食用动物生产是否构成重大风险 对于AMR向儿童的传播，控制其他已知的风险因素，在目标3b中，我们将应用 定性研究方法来表征小规模食用动物中抗菌剂使用的驱动因素 生产预期成果：据我们所知，拟议的研究将是同类研究中的第一项， 这可能会为未来旨在更好地了解AMR社区传播的研究开创先例。这 这项研究可能会对我们理解以下问题做出重大贡献：i）AMR的机制问题 传播（即克隆传播与水平基因转移）; ii）AMR的确定性相关问题 传播（即与MDR/ESBL-E定植相关的风险因素）。（iii）了解 在小规模食用动物生产中使用抗菌剂的驱动因素。

Project Summary/Abstract The increased prevalence of antimicrobial resistance (AMR) among Enterobacteriaceae has had major clinical and economic impacts in human medicine. Many of the multi-drug resistant (MDR) Enterobacteriaceae found in humans are community-acquired and linked to food-animals (i.e. livestock raised for meat and dairy products). The objective of this research project is to apply epidemiologic methods and next-generation DNA sequencing to quantify the exchange of MDR strains of E. coli and mobile genetic elements (e.g. plasmids, transposons, etc.) between food-animals and children living in peri-urban parishes east of Quito, Ecuador where small-scale food-animal production is widespread. The study will include households with young children in three neighborhood types: 1) neighborhoods with no food-animal production; 2) neighborhoods with small-scale food-animal production only; and 3) neighborhoods with small-scale and commercial-scale food- animal production. Approach: In Aim 1, we will examine whether young children and food-animals share E. coli clones [assessed by whole genome multi-locus sequence typing (wgMLST)] that also have the same phenotypic multi-drug resistance pattern. In Aim 2, we will identify MDR E. coli strains in young children and animals that are not clones (identified by wgMLST) but share the same phenotypic multi-drug resistance pattern. We will then analyze the mobile genetic elements associated with the observed phenotypic resistance patterns and characterize the phylogenetic relationship of the mobile genetic elements responsible for resistance gene transfer. In Aim 3a, we will examine whether food-animal production poses a significant risk for transmission of AMR to children, controlling for other known risk factors, and in Aim 3b, we will apply qualitative research methods to characterize the drivers of antimicrobial use in small-scale food-animal production. Expected Outcomes: To our knowledge, the proposed study will be one of the first of its kind and will likely set a precedent for future studies that aim to better understand community transmission of AMR. This study will likely make major contributions to our understanding of: i) mechanistic questions of AMR transmission (i.e. clonal spread versus horizontal gene transfer); ii) exposure-related questions of AMR transmission (i.e. risk factors associated with colonization with MDR/ESBL-E. coli); and iii) an understanding of the driving factors for use of antimicrobials in small-scale food-animal production.