Novel inter-disciplinary approaches for identifying and tackling the spread of AntiMicrobial Resistance through Environmental pathways in PAKistan

巴基斯坦通过环境途径识别和应对抗菌素耐药性传播的新型跨学科方法

基本信息

批准号：
MR/R015058/1
负责人：
Christopher Quince
金额：
$ 10.25万
依托单位：
University of Warwick
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FR015058%2F1
关键词：
Novel inter disciplinary approaches identifying

项目摘要

Medicine has been transformed by the development of antibiotics, medicines that kill bacteria. These have made deadly bacterial diseases that once killed millions such as tetanus, syphilis, and leprosy, easily treatable. They are given as a preventative measure prior to surgery to prevent infection and they relieve suffering from less dangerous diseases such as strep throat. There is, however, a problem. Bacteria are becoming resistant to antibiotics. This is a result of evolution. The use of antibiotics inevitably selects for bacteria that carry genes that can protect them against these compounds. We call these antibiotic or antibacterial resistance genes (ARGs). Genes are pieces of DNA that make up part of the bacteria's genome or smaller DNA molecules such as plasmids. ARGs provide bacteria with the ability to degrade or excrete antibiotics. They can be exchanged between different species of bacteria allowing these abilities to spread through communities.The use and misuse of antibiotics is accelerating the rate at which ARGs evolve and spread. Using antibiotics to treat non-bacterial infections or to improve the growth rate of livestock results in large amounts of antibiotics entering the environment, this creates a strong selective pressure leading to many resistant bacteria. This resistance can develop in free-living bacteria that perform important functions in ecosystems, e.g. soils or rivers, but then spread to bacteria that cause disease within humans, pathogens. There are pathogens beginning to appear that are resistant to multiple antibiotics, e.g. multidrug-resistant tuberculosis. If this multi-drug resistance spreads further then diseases that are now treatable will become increasingly deadly. This is a potential global public health disaster. The problems caused by antibiotic resistance (ABR) will particularly badly impact Low and Middle Income Countries (LMICs), such as Pakistan, that depend upon cheap antibiotics to treat many infectious diseases. Tragically, it is just these countries, which are likely to have the most problems. This is because antibiotics are easily available without prescription over the counter. People take antibiotics to treat non-bacterial diseases or do not take them for long enough, this allows the resistant bacteria to spread and proliferate. This is compounded by manufacturers of antibiotics releasing wastewater contaminated with antibiotics into the environment, farmers using large quantities of antibiotics in intensive livestock rearing, and the fact that human and animal waste is dumped untreated into water sources. All this pollution results in more resistant bacteria evolving. It is unclear, however, which of these factors are most important to address, in order to prevent the spread of ABR.We have assembled a team of biologists, engineers, social scientists and mathematicians, to better understand ABR in Pakistan and how to combat it. We will conduct a survey of resistance genes across multiple areas within Pakistan, chosen in order to determine what causes them to proliferate and spread, ultimately leading to drug-resistant infections in humans. We will do this by sequencing DNA direct from environmental samples to resolve the genes that are present in the bacteria. We will sample from the environment and from a range of health facilities to reveal how genes are being transmitted from environmental bacteria into pathogens. We will also study the behaviour of people and institutions in Pakistan and determine how that contributes to the scale of the problem. This will allow us to propose ways in which they can reduce the spread of antibiotic resistant genes. These might be changes to how antibiotics are used in health facilities or improved approaches to waste disposal. This will be of great benefit to Pakistan but also - because these genes are capable of spreading between individuals across the world - to other LMICs and us in the UK too.

抗生素和杀死细菌的药物的发展改变了医学。这些使得破伤风、梅毒和麻风病等曾经导致数百万人死亡的致命细菌性疾病变得容易治疗。它们作为手术前的预防措施来预防感染，并减轻链球菌性咽喉炎等不太危险的疾病的痛苦。然而，有一个问题。细菌对抗生素产生耐药性。这是进化的结果。抗生素的使用不可避免地会选择携带可以保护它们免受这些化合物侵害的基因的细菌。我们将这些称为抗生素或抗菌素耐药基因（ARG）。基因是构成细菌基因组一部分的 DNA 片段或较小的 DNA 分子（例如质粒）。 ARG 为细菌提供了降解或分泌抗生素的能力。它们可以在不同种类的细菌之间交换，从而使这些能力在群落中传播。抗生素的使用和滥用正在加速 ARG 的进化和传播速度。使用抗生素治疗非细菌感染或提高牲畜生长速度，会导致大量抗生素进入环境，产生强大的选择压力，导致许多耐药细菌产生。这种抵抗力可以在自由生活的细菌中产生，这些细菌在生态系统中发挥着重要的作用，例如：土壤或河流，但随后传播到导致人类疾病的细菌，即病原体。有些病原体开始出现对多种抗生素具有抗药性，例如抗生素。耐多药结核病。如果这种多重耐药性进一步蔓延，那么现在可以治疗的疾病将变得越来越致命。这是一场潜在的全球公共卫生灾难。抗生素耐药性（ABR）引起的问题将对中低收入国家（LMIC）产生特别严重的影响，例如巴基斯坦，这些国家依赖廉价抗生素来治疗许多传染病。可悲的是，正是这些国家可能面临最多的问题。这是因为无需处方即可在柜台轻松获得抗生素。人们服用抗生素来治疗非细菌性疾病，或者服用时间不够长，这会导致耐药细菌传播和增殖。抗生素制造商将受抗生素污染的废水排放到环境中，农民在集约化牲畜饲养中使用大量抗生素，以及人类和动物废物未经处理就倾倒到水源中，使情况变得更加复杂。所有这些污染都会导致更多耐药细菌的进化。然而，为了防止 ABR 的传播，目前尚不清楚这些因素中哪一个最需要解决。我们组建了一个由生物学家、工程师、社会科学家和数学家组成的团队，以更好地了解巴基斯坦的 ABR 以及如何应对它。我们将对巴基斯坦境内多个地区的耐药基因进行调查，选择这些基因是为了确定是什么导致它们增殖和传播，最终导致人类产生耐药性感染。为此，我们将直接对环境样本中的 DNA 进行测序，以解析细菌中存在的基因。我们将从环境和一系列卫生设施中取样，以揭示基因如何从环境细菌传播到病原体。我们还将研究巴基斯坦人民和机构的行为，并确定其如何导致问题的严重程度。这将使我们能够提出减少抗生素抗性基因传播的方法。这些可能是医疗机构中抗生素使用方式的改变或废物处理方法的改进。这不仅对巴基斯坦有很大好处，而且对其他中低收入国家和我们英国也有很大好处，因为这些基因能够在世界各地的个体之间传播。