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

抗生素的发展改变了医学，抗生素是杀死细菌的药物。这使得曾经导致数百万人死亡的致命细菌性疾病，如破伤风、梅毒和麻风病，变得容易治疗。它们是作为手术前的预防措施，以防止感染，并减轻危险性较低的疾病，如链球菌性咽喉炎的痛苦。然而，有一个问题。细菌对抗生素产生了抗药性。这是进化的结果。抗生素的使用不可避免地选择了携带基因的细菌，这些基因可以保护它们免受这些化合物的侵害。我们称之为抗生素或抗菌素抗性基因（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，如质粒。ARG为细菌提供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，使这些能力在社区中传播。抗生素的使用和滥用正在加速ARG进化和传播的速度。使用抗生素治疗非细菌性感染或提高牲畜的生长速度，导致大量抗生素进入环境，这产生了强大的选择压力，导致许多耐药细菌。这种耐药性可以在生态系统（例如土壤或河流）中发挥重要作用的自由生活的细菌中发展，但随后传播给引起人类疾病的细菌，即病原体。开始出现对多种抗生素具有耐药性的病原体，例如耐多药结核病。如果这种多药耐药性进一步蔓延，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）引起的问题将特别严重地影响巴基斯坦等依赖廉价抗生素治疗许多传染病的中低收入国家（LMIC）。可悲的是，正是这些国家可能面临最多的问题。这是因为抗生素很容易获得，无需处方。人们服用抗生素来治疗非细菌性疾病，或者没有服用足够长的时间，这使得耐药细菌传播和繁殖。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在水源中，使情况更加复杂。所有这些污染导致更多的耐药细菌进化。然而，目前还不清楚，为了防止ABR的传播，这些因素中哪些是最重要的。我们已经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以及如何对抗它。我们将在巴基斯坦多个地区进行耐药基因调查，以确定是什么导致它们扩散和传播，最终导致人类的抗药性感染。我们将通过直接从环境样本中测序DNA来解决细菌中存在的基因。我们将从环境和一系列卫生设施中取样，以揭示基因是如何从环境细菌传播到病原体的。我们还将研究巴基斯坦人民和机构的行为，并确定这如何导致问题的严重性。这将使我们能够提出减少抗生素耐药基因传播的方法。这些可能是改变抗生素在卫生设施中的使用方式或改进废物处理方法。这将对巴基斯坦有很大的好处，而且--因为这些基因能够在世界各地的个人之间传播--对其他中低收入国家和我们英国人也有好处。

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.