NEC05839 Chicken or the Egg: Is AMR in the Environment Driven by Dissemination of Antibiotics or Antibiotic Resistance Genes?

NEC05839 先有鸡还是先有蛋：环境中的抗菌素耐药性是由抗生素或抗生素抗性基因的传播驱动的吗？

• 批准号: NE/N019687/2
• 负责人: Andrew Singer
• 金额: $ 10万
• 依托单位: UK CENTRE FOR ECOLOGY & HYDROLOGY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=NE%2FN019687%2F2
• 关键词: NEC05839; Chicken; Egg; AMR; Environment

Antimicrobial resistance (AMR) in the environment is driven by antibiotics released in the urine of humans and animals into sewage and ultimately the receiving rivers. AMR is also released from within the gut bacteria that are shed in faeces of both humans and animals. In both cases, antibiotics and AMR-containing gut bacteria are released into the environment through sewage. Despite the continued release of both antibiotics and antibiotic-resistant bacteria into our rivers, we still don't know the relative role that they play in explaining the amount of antibiotic resistance that we see in our environment. This is a critically important knowledge gap as it prevents industry and policy makers from determining where to spend our time and resources so as to lower this 'environmental reservoir of antimicrobial resistance'.Sewage contains thousands of chemicals, many of which are at concentrations sufficient to inhibit or kill bacteria. Microbes defend themselves from these chemicals with a range of strategies, all of which have genes that are broadly classified as 'resistance genes'. Hence, sewage is an excellent place to find bacteria rich in resistance genes. Many of these genes are known to be mobile, which allows for the genes to be shared, thereby increasing its abundance within the environment. This mobility of genes is key to why it is so difficult to know what is driving AMR in the environment-a bit like 'which came first, the chicken or the egg.' Are the concentrations of antibiotics present in sewage sufficiently high to select for resistance genes in the environment or are the genes for resistance simply spreading from the gut-derived bacteria into the native environmental microorganisms? The keys to answering this question lie in the following two questions: 1) Do genes released from sewage move into and persist in the natural microbial community without continued exposure to critical threshold concentrations of antibiotics; and 2) Are the critical threshold concentrations in the environment sufficiently high to maintain gut-derived AMR genes in the natural microbial community or select for them all on their own?In the proposed research we aim to answer these two key questions using four innovative experimental systems: 1) a small laboratory microfluidic system for the precise control and manipulation of microbial biofilms; 2) an in situ river mesocosm and 3) ex situ macrocosm which can also control and manipulate microbial biofilms under controlled conditions with the addition of antibiotics and/or antibiotic resistance genes; and finally 4) the use of the freshwater shrimp, Gammarus pulex, as an indicator species of environments where the reservoir of antibiotic resistance is elevated. In the case of the Gammarus, we will study the microorganisms that live within this shrimp and determine if these microbes acquire similar antibiotic resistance traits as those found in identically-exposed biofilms. Modern molecular techniques (i.e, metagenomes, plasmid metagenomes, qPCR, meta-transcriptomes), will be used to quantify treatment effects within biofilms and Gammarus. The data from these studies will be used to parameterise a mathematical/statistical model that will be designed for use by regulators, industry and academia to better predict and understand the risks posed by AMR in the environment.

环境中的抗菌耐药性（AMR）是由人类和动物尿液中释放的抗生素驱动的，并最终将接收河流造成。 AMR还从肠道细菌中释放出来，这些细菌均在人类和动物的粪便中释放。在这两种情况下，抗生素和含AMR的肠道细菌都通过污水释放到环境中。尽管抗生素和抗生素耐药细菌持续释放到我们的河流中，但我们仍然不知道它们在解释我们在环境中看到的抗生素抗性量中所起的相对作用。这是一个至关重要的知识差距，因为它可以防止行业和政策制定者确定在哪里花费我们的时间和资源，以降低这种“抗菌耐药的环境储层”。少数含有成千上万种化学物质，其中许多化学物质足以抑制或杀死细菌。微生物通过一系列策略为这些化学物质辩护，所有这些化学物质都具有广泛归类为“抗性基因”的基因。因此，污水是找到富含耐药基因的细菌的好地方。这些基因中的许多都是可移动的，它允许共享基因，从而增加了环境中其丰度。基因的这种流动性是为什么很难知道在环境中驱动AMR的原因是“首先是鸡肉或鸡蛋”。污水中存在抗生素的浓度是否足够高以选择环境中的抗性基因，还是耐药基因仅仅从肠道衍生的细菌传播到天然环境微生物中？回答这个问题的关键在于以下两个问题：1）从污水中释放的基因转移到自然微生物群落中，而不会继续暴露于抗生素的关键阈值浓度； 2）环境中的临界阈值浓度是否足够高，可以保持天然微生物群落中的肠道衍生AMR基因或自行选择它们？在拟议的研究中，我们旨在使用四个创新的实验系统回答这两个关键问题：1）一个小型实验室微流体系统，用于对微生物的精确控制和操纵微生物的机制； 2）原位中河中心和3）在受控条件下还可以通过添加抗生素和/或抗生素抗性基因来控制和操纵微生物生物膜；最后4）使用淡水虾Pulex的使用，作为抗生素耐药性储层的环境的指标。在伽马鲁斯的情况下，我们将研究生活在该虾中的微生物，并确定这些微生物是否获得了与相同暴露的生物膜相同的抗生素耐药性状。现代分子技术（即元基因组，质粒元基因组，QPCR，元转录组）将用于量化生物膜和伽马鲁斯中的治疗效果。这些研究的数据将用于参数化数学/统计模型，该模型将设计用于监管机构，行业和学术界，以更好地预测和理解AMR在环境中带来的风险。

项目成果

Setting the agenda for social science research on the human microbiome

• DOI: 10.1057/s41599-020-0388-5
• 发表时间: 2020-01-31
• 期刊: PALGRAVE COMMUNICATIONS
• 影响因子: 4
• 作者: Greenhough, Beth;Read, Cressida Jervis;Wills, Jane
• 通讯作者: Wills, Jane

Author Correction: Detection of untreated sewage discharges to watercourses using machine learning

作者更正：使用机器学习检测未经处理的污水排放到水道

• DOI: 10.1038/s41545-021-00116-3
• 发表时间: 2021
• 期刊: npj Clean Water
• 影响因子: 11.4
• 作者: Hammond P

Campaign-Based Citizen Science for Environmental Mycology: the "Science Solstice" and "Summer Soil-stice" Projects to Assess Drug Resistance in Air and Soilborne Aspergillus fumigatus

基于运动的环境真菌学公民科学：评估空气和土传烟曲霉耐药性的“Science Solstice”和“Summer Soil-stice”项目

• DOI: 10.1101/2020.06.11.146241
• 发表时间: 2020
• 作者: Shelton J

Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy.

• DOI: 10.1136/bmjgh-2020-003091
• 发表时间: 2020-09
• 期刊: BMJ global health
• 影响因子: 8.1
• 作者: Kirchhelle C;Atkinson P;Broom A;Chuengsatiansup K;Ferreira JP;Fortané N;Frost I;Gradmann C;Hinchliffe S;Hoffman SJ;Lezaun J;Nayiga S;Outterson K;Podolsky SH;Raymond S;Roberts AP;Singer AC;So AD;Sringernyuang L;Tayler E;Rogers Van Katwyk S;Chandler CIR
• 通讯作者: Chandler CIR

NIMble innovation - a networked model for public antibiotic trials

NIMble 创新 - 公共抗生素试验的网络模型

• DOI: 10.31235/osf.io/vp8mj
• 发表时间: 2021
• 作者: Glover R