Establishing drivers for the generation and transmission of antimicrobial resistance in the food chain

确定食物链中抗菌素耐药性产生和传播的驱动因素

• 批准号: 2302676
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2302676
• 关键词: Establishing; drivers; generation; transmission; antimicrobial

Pathogenic microorganisms pose a significant threat to food security and in the spread of infectious diseases, particularly where the transmission of antibiotic resistant organisms (ARO) remains a critical concern. The drivers for the selection or maintenance of ARO's within the environment represents an important route for the dissemination of these organisms via the food chain. As such, the occurrence and presence of ARO's in the environment can arise simply as a result of selection by endogenous antibiotics, or the application of antibiotic or antibiotic-like compounds within the environment. As such, recent data reveals that the genetic factors which contribute to pesticide resistance also confer antibiotic resistance. Despite this evidence, little is known about the impact of pesticide exposure and the potential for the development of antimicrobial resistance in common microorganisms found within the food chain. In this application, our overarching aim is to establish a mechanistic basis for pesticide exposure and the transfer of AMR organisms from the environment into the food supply; where the specific aims are to:Aim 1: To establish a "colonisation & pesticide resistance" plant model system, we will use a genetically tractable model, which will exploit a relevant edible horticultural species subject to common pesticide treatment (glyphosate), inoculated with two microbial species associated with antimicrobial resistance (Kpn) and foodborne transmission (Eco O157:H7). This model system will be used to parameterise the conditions of in vivo colonisation such as bacterial colonisation versus time, pesticide concentrations to elicit adaptive genetic changes.Aim 2: To establish the mechanistic basis of pesticide resistance, wholescale adaptive changes after pesticide exposure will be determined from the optimised model system, by both whole genome sequence analysis and transcriptome (RNA-seq) profiling. This will establish both, which genes represent mutational hot-spots and regulatory networks are altered, thus facilitating an integrated network of genetic changes to be mapped and linked to the antibiotic/pesticide resistance phenotype.Aim 3: Determine if pesticide exposure accelerates the acquisition of antimicrobial and pesticide resistance. Using the in-vivo model, the genetic and phenotypic properties of the focal species e.g, Kpn or Eco O157:H7 will be established in the presence or absence of pesticides and exogenous AMR bacteria e.g. animal manure. This will establish whether adaptation to pesticides can accelerate the acquisition or horizontal transfer of resistance elements from exogenous sources. The expected outcomes will be the validation and implementation of an in-vivo plant microbe colonisation model to assess the contributions of pesticide use in promoting microorganism and ARO transfer.

病原微生物对粮食安全和传染病的传播构成重大威胁，特别是在抗生素耐药生物体（ARO）的传播仍然是一个严重问题的情况下。在环境中选择或维持ARO的驱动因素代表了这些生物通过食物链传播的重要途径。因此，ARO在环境中的出现和存在可以简单地由于内源性抗生素的选择或环境中抗生素或类抗生素化合物的应用而产生。因此，最近的数据表明，导致杀虫剂抗性的遗传因素也会产生抗生素抗性。尽管有这些证据，但人们对农药暴露的影响以及食物链中常见微生物产生抗菌素耐药性的可能性知之甚少。在本申请中，我们的总体目标是建立农药暴露和AMR生物从环境转移到食品供应的机制基础;具体目标是：目标1：为了建立一个“定殖&农药抗性”植物模型系统，我们将使用一个遗传上易于处理的模型，该模型将利用相关的食用园艺物种进行常规农药处理（草甘膦），接种两种与抗菌剂耐药性（Kpn）和食源性传播（Eco O 157：H7）相关的微生物菌种。该模型系统将被用来参数化的条件下，在体内定植，如细菌定植与时间，农药浓度，以引起适应性genetic changes.Aim 2：为了建立农药抗性的机制的基础上，大规模的适应性变化农药暴露后，将确定从优化的模型系统，通过全基因组序列分析和转录组（RNA-seq）分析。这将建立两个，哪些基因代表突变的热点和监管网络被改变，从而促进一个综合网络的遗传变化被映射和链接到抗生素/农药抗性phenotype.Aim 3：确定农药暴露是否加速收购抗菌药物和农药抗性。使用体内模型，将在存在或不存在农药和外源AMR细菌（例如动物粪便）的情况下确定重点种属（例如Kpn或Eco O 157：H7）的遗传和表型特性。这将确定对农药的适应是否可以加速从外源获得或横向转移抗性元素。预期的成果将是验证和实施一个体内植物微生物定殖模型，以评估农药的使用在促进微生物和ARO转移的贡献。