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

总体研究：我们并不完全了解编码抗生素耐药性的重要细菌类型（物种）和遗传物质包（基因）如何在人类、动物和环境之间移动，或者抗生素耐药性在哪里、如何以及为什么出现。本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，以找出重要抗生素耐药细菌和抗生素耐药基因的复杂传播网络。我们将利用这些信息找出减缓抗生素耐药性在人类、牲畜和环境之间传播的最佳方法。更详细的研究背景和目的感染是人类和动物医学中最常见的健康不良原因之一，由一系列不同的微生物引起，包括病毒和细菌。在细菌中，有一些种类或类型的细菌，它们可以在人类和动物的肠道、污水和河流中无害地生活，但如果它们进入了错误的身体空间，比如血液或尿液，也会导致人类和动物生病。这些细菌的例子包括大肠杆菌和其他类似的有机体，它们属于被称为“肠杆菌科”的细菌家族。一般来说，使用几种被称为抗生素的药物来治疗由细菌引起的感染是可能的。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，或者它们可以分解细菌的外壳。作为对抗生素使用的反应，细菌随着时间的推移发生了变化，它们找到了改变自身结构的方法，使抗生素不再有作用的目标，或者通过产生在抗生素有机会杀死细菌之前分解抗生素的物质。这些细菌遗传密码的改变，使它们不再被抗生素杀死，从而产生了抗生素耐药性。细菌还可以从周围的其他细菌那里获得导致抗生素耐药性的基因包。这被称为水平基因转移。通过这些机制，肠杆菌科细菌家族的成员在短时间内对许多不同的抗生素产生了耐药性。在某些情况下，我们不再能够用现有的抗生素治疗这些感染。研究在人类、动物和环境中发现的细菌的抗生素耐药性和水平基因转移是困难的，因为我们不能直接看到细菌及其遗传物质如何在它们之间移动。然而，新的“下一代测序”（NGS）技术使科学家能够非常详细地观察大量细菌的遗传密码。通过比较生活在环境不同部分（如污水处理厂、河流）以及人类和动物污水中的细菌的这些信息，我们可以看到细菌是如何进化成对抗生素具有耐药性的，以及它们之间是如何共享耐药性基因的。这项研究将使用NGS技术来研究在人类、动物（猪、羊和家禽）、污水（处理前、处理中和处理后）和河流中发现的大量肠杆菌科细菌的遗传密码。将在一个日历年的不同季节对这些不同的群体/地区进行采样，以确定抗生素抗性基因如何在这些地点和时间之间移动，以及哪些因素可能影响这种移动。我们还将调查水中的各种化学物质和营养物质是否会影响水平基因转移发生的速度。了解这一点对于我们如何更有效地干预以减缓抗生素抗性基因和细菌的传播，并保持抗生素药物的有效性至关重要。

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.