NEC05836 The environmental REsistome: confluence of Human and Animal Biota in antibiotic resistance spread (REHAB)

NEC05836 环境 REsistome：人类和动物生物群在抗生素耐药性传播中的汇合 (REHAB)

• 批准号: NE/N019660/1
• 负责人: Daniel Read
• 金额: $ 24.63万
• 依托单位: NERC CEH (Up to 30.11.2019)
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FN019660%2F1
• 关键词: NEC05836; environmental; REsistome; confluence; Human

OVERALL STUDY AIMWe do not fully understand how important types (species) of bacteria and packages of genetic material (genes) coding for antibiotic resistance move between humans, animals and the environment, or where, how and why antibiotic resistance emerges. This study aims to look in detail at the genetic level at bacteria in farm animals, human/animal sewage, sewage treatment works and rivers, to work out the complex network of transmission of important antibiotic-resistant bacteria and antibiotic resistance genes. We will use this information to work out how best to slow down the spread of antibiotic resistance between humans, livestock and the environment. STUDY BACKGROUND AND AIMS IN MORE DETAILInfections are one of the most common causes of ill-health in human and animal medicine, and are caused by a range of different micro-organisms, including viruses and bacteria. Amongst bacteria, there are some species, or types, of bacteria, which can live harmlessly in human and animal intestines, sewage, and rivers, but can also cause disease in humans and animals if they get into the wrong body space, such as the bloodstream or urine. Examples of these bacteria include E. coli, and other similar organisms, which belong to a family of bacteria called "Enterobacteriaceae".It has generally been possible to treat infections caused by bacteria using several classes of medicines, known as antibiotics. Different antibiotics kill bacteria in different ways: for example, they can switch off critical chemical processes that the bacteria need to survive, or they can break down the outer shell of the bacteria. In response to the use of antibiotics, bacteria have changed over time, finding ways to alter their structure so that antibiotics no longer have a target to act on, or by producing substances that break down the antibiotic before it has a chance to kill the bacteria. These changes to the bacteria's genetic code, so that they are no longer killed by an antibiotic, create antibiotic resistance. Bacteria can also acquire packages of genes that cause antibiotic resistance from other surrounding bacteria. This is known as horizontal gene transfer. Through these mechanisms, members of the Enterobacteriaceae family of bacteria have developed antibiotic resistance to a number of different antibiotics over a short period of time. In some cases we are no longer able to treat these infections with the antibiotics we have available. Studying antibiotic resistance and horizontal gene transfer in bacteria found in humans, animals and the environment is difficult because we cannot directly see how bacteria and their genetic material move between them. However, new "Next Generation Sequencing" (NGS) technologies allow scientists to look in great detail at the genetic code of large numbers of bacteria. Comparing this information across bacteria which have been living in the different parts of the environment (e.g. sewage treatment works, rivers) and in human and animal sewage allows us to see how bacteria have evolved to become resistant to antibiotics, and how resistance genes have been shared between them. This study will use NGS technologies to look at the genetic code of large numbers of Enterobacteriaceae bacteria found in humans, animals (pigs, sheep and poultry), sewage (pre-, during and post-treatment), and rivers. These different groups/areas will be sampled in different seasons of one calendar year to determine how antibiotic resistance genes move around between these locations and over time, and what factors might influence this movement. We will also be investigating whether various chemicals and nutrients in the water may be affecting how quickly horizontal gene transfer occurs. Understanding this is essential to work out how we might intervene more effectively to slow the spread of antibiotic resistance genes and bacteria, and keep our antibiotic medicines useful.

总体研究目标我们不完全了解细菌的重要类型（种类）和编码抗生素耐药性的遗传物质（基因）如何在人类，动物和环境之间移动，或者在哪里，如何以及为什么出现抗生素耐药性。这项研究旨在详细研究农场动物，人/动物污水，污水处理厂和河流中细菌的遗传水平，以确定重要的抗生素耐药菌和抗生素耐药性基因的复杂传播网络。我们将使用这些信息来阐明如何最好地减缓人类，牲畜和环境之间抗生素耐药性的传播。研究背景和旨在更详细的发现是人类和动物医学​​中最常见的健康原因之一，是由包括病毒和细菌在内的一系列不同的微生物引起的。在细菌中，有一些细菌或类型的细菌，它们可能在人类和动物肠道，污水和河流中无害地生活，但如果它们进入错误的身体空间，例如血液或尿液或尿液，也可能引起人类和动物的疾病。这些细菌的例子包括大肠杆菌和其他类似的生物，这些生物属于一个称为“肠杆菌科”的细菌家族。通常，使用几种类型的药物（称为抗生素）来治疗由细菌引起的感染。不同的抗生素以不同的方式杀死细菌：例如，它们可以关闭细菌生存所需的关键化学过程，或者可以分解细菌的外壳。为了响应抗生素的使用，细菌随着时间的流逝而改变，找到改变其结构的方法，以使抗生素不再具有作用的靶标，或者通过产生在有机会杀死细菌之前分解抗生素的物质。这些改变了细菌的遗传密码，因此它们不再被抗生素杀死，会产生抗生素耐药性。细菌还可以获取从其他周围细菌引起抗生素耐药性的基因包装。这被称为水平基因转移。通过这些机制，细菌肠杆菌科家族的成员在短时间内对多种不同的抗生素产生了抗生素抗性。在某些情况下，我们不再能够使用可用的抗生素来治疗这些感染。在人类，动物和环境中发现抗生素耐药性和水平基因转移非常困难，因为我们无法直接看到细菌及其遗传物质如何在它们之间移动。但是，新的“下一代测序”（NGS）技术使科学家可以详细介绍大量细菌的遗传密码。比较生活在环境不同部位（例如污水处理工作，河流）和人类和动物污水中的细菌中的这些信息，使我们能够看到细菌如何进化以抗抗生素的抗性，以及它们之间如何共享抗性基因。这项研究将使用NGS技术来研究人类，动物（猪，绵羊和家禽），污水（治疗前和河流）和河流中发现的大量肠杆菌科细菌的遗传密码。这些不同的组/区域将在一个日历年的不同季节中进行采样，以确定抗生素抗性基因如何在这些位置和随着时间的流逝之间移动，以及哪些因素可能影响这一运动。我们还将研究水中的各种化学物质和营养是否可能影响水平基因转移的发生速度。理解这对于确定我们如何更有效地干预以减缓抗生素耐药性基因和细菌的传播，并保持我们的抗生素药物有用。

项目成果

Comparison of long-read sequencing technologies in the hybrid assembly of complex bacterial genomes

复杂细菌基因组混合组装中长读长测序技术的比较

• DOI: 10.1101/530824
• 发表时间: 2019
• 作者: De Maio N

The impact of sequencing depth on the inferred taxonomic composition and AMR gene content of metagenomic samples

测序深度对宏基因组样本推断分类组成和AMR基因含量的影响

• DOI: 10.1101/593301
• 发表时间: 2019
• 作者: Gweon H

Systematic review of wastewater surveillance of antimicrobial resistance in human populations

• DOI: 10.20944/preprints202010.0267.v2
• 发表时间: 2021-06
• 期刊: Environment International
• 影响因子: 11.8
• 作者: K. Chau;L. Barker;E. Budgell;K. Vihta;N. Sims;B. Kasprzyk-Hordern;E. Harriss;D. Crook;D. Read;S. Walker;N. Stoesser

Wastewater Surveillance of Antimicrobial Resistance in Human Populations: A Systematic Review

• DOI: 10.20944/preprints202010.0267.v1
• 发表时间: 2020-10
• 作者: K. Chau;L. Barker;N. Sims;B. Kasprzyk-Hordern;E. Budgell;E. Harriss;D. Crook;D. Read;S. Walker;N. Stoesser

MOESM2 of The impact of sequencing depth on the inferred taxonomic composition and AMR gene content of metagenomic samples

MOESM2 测序深度对宏基因组样本推断分类组成和 AMR 基因含量的影响

• DOI: 10.6084/m9.figshare.10049006
• 发表时间: 2019
• 作者: H. Gweon