MEtaGenome-informed Antimicrobial resistance Surveillance: Harnessing long-read sequencing for an analytical, indicator and risk assessment framework

基于 MEtaGenome 的抗菌药物耐药性监测：利用长读长测序构建分析、指标和风险评估框架

• 批准号: MR/Y034457/1
• 负责人: Alison Mather
• 金额: $ 46.69万
• 依托单位: Quadram Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY034457%2F1
• 关键词: MEtaGenome; informed; Antimicrobial; resistance; Surveillance

Antimicrobial resistance (AMR) is a threat to humans, animals, and crops, and requires a coordinated One Health approach. AMR affects many of the goals of the WHO 2030 Agenda for Sustainable Development. Levels of AMR are generally quantified by culturing indicator organisms like E. coli, and determining its resistance. Looking at only one indicator organism in all human, animal, food and environmental samples is like studying ocean life by looking at a single droplet of seawater with a microscope. Interesting differences can be found between droplets but is it really the entire picture?Metagenomic sequencing is a technique that allows identification and quantification of AMR genes and species in a sample without culturing. Currently the use of short read sequencing is more common but limited when AMR quantification is required. One can only quantify genes, not where they are. On a chromosome? Or in a transmittable plasmid or transposon, which can easily spread to pathogens?We propose to use long-read Nanopore sequencing to develop a 'one stop shop' surveillance method. Long reads contain both resistance genes and flanking sequences, thereby identifying the original organism or mobile genetic element, the location, but also genes associated with high transmission risk. We propose integrating into traditional methods to expand surveillance into non-model-organisms.By working with stakeholders in government, industry and academia, this project will support translation of long-read metagenome data into actionable surveillance information for the reduction of risk to human health.

抗生素耐药性（AMR）是对人类、动物和作物的威胁，需要采取协调一致的“一个健康”方法。AMR影响到世卫组织2030年可持续发展议程的许多目标。AMR的水平通常通过培养指示生物如大肠杆菌来定量。大肠杆菌，并测定其耐药性。在所有人类、动物、食物和环境样本中只观察一种指示生物，就像用显微镜观察一滴海水来研究海洋生物一样。在液滴之间可以发现有趣的差异，但这真的是全部吗？宏基因组测序是一种无需培养即可鉴定和定量样品中AMR基因和物种的技术。目前，短读测序的使用更常见，但在需要AMR定量时受到限制。人们只能量化基因，而不能量化它们在哪里。在染色体上？还是在一个可传播的质粒或转座子中，它可以很容易地传播给病原体？我们建议使用长读纳米孔测序来开发“一站式”监测方法。长读段既包含抗性基因又包含侧翼序列，从而识别原始生物体或移动的遗传元件的位置，而且还识别与高传播风险相关的基因。通过与政府、产业界和学术界的利益相关者合作，该项目将支持将长期阅读的宏基因组数据转化为可操作的监测信息，以减少对人类健康的风险。