Does the potential for AMR selection differ between common UK cattle grazing systems?

抗菌素耐药性（AMR）的发生是因为反复接触抗菌素药物杀死了敏感细菌，使耐药类型繁殖。最近关于致病细菌对抗生素产生耐药性对人类健康造成毁灭性后果的引人注目的报告强调，有必要了解导致人类和动物病原体中抗菌素耐药性日益普遍的过程。农场动物被认为是抗生素耐药性的主要来源，因为用于治疗感染（治疗性使用）和预防感染（预防性使用）的大量抗生素。然而，人们对农业系统中的耐药性背景水平知之甚少，即使动物只在需要抗生素时（治疗性地）使用抗生素。例如，相近的细菌共享遗传物质是另一种途径，抗菌素耐药性可能在其他不相关的细菌中意外出现。当牛靠近时，例如在冬季圈养期间，它们之间的抗菌素耐药性传播可能更大。在这个提议中，我们将使用一个实验农场，在那里饲养的牛肉只接受兽医称之为“最佳实践”的最低限度的抗生素治疗。在夏季放养和冬季放养时分别监测牛粪中AMR细菌和基因的动态变化。我们将仔细监测那些患病并服用抗生素的牛和其他牛群。农场动物的饮食也可能影响其肠道菌群中AMR的增加。即使是牛在外出放牧时通常吃的草和三叶草等普通植物（“饲料”）也会产生天然的抗菌化合物，这些化合物可能在胃（瘤胃）中继续活跃，而瘤胃中有数百万细菌繁殖和繁殖。在冬天，牛被带到室内喂养青贮饲料，这是一种经过发酵保存的草地植物。未消化的食物和来自瘤胃的大量细菌，因此可能是抗菌素耐药性，在牛粪中排泄。我们将分析食用不同饲料类型的牛的粪便，以找出它们所吃的饲料是否会影响食用一种饲料的牛与食用另一种饲料的牛发生抗菌素耐药性的可能性。英国的大多数养牛场都位于多山的“潮湿的西部”，那里雨水将农田径流到水道中的可能性很高。由于气候变化，导致大量径流和洪水的最近暴风雨的增加预计将继续下去。与此同时，近年来越来越多的人认识到，抗菌素耐药性可能出现在农场动物身上，并从农场环境中释放到水中的自然环境中，最终可能进入饮用水、洗澡水或海鲜中。通常，使用粪便指示生物（FIOs）来监测水中牛粪的污染，这些细菌通常不会引起疾病，但与引起疾病的细菌（病原体）相关，并且可以由科学家安全地处理。了解fio中携带抗菌素耐药性的比例将是有用的，因为它们是常规检测的，有助于将来估计抗菌素耐药性的传播。我们将对从被肉牛放牧或用牛粪传播的田地流出的水进行取样，并分析水中的细菌，包括fio，看看它们是否对抗生素具有耐药性。这项研究的结果应该有助于我们了解在牛群中产生的抗菌素耐药性是否可能转移到环境中，管理是否可以限制抗菌素耐药性及其传播，并为评估新抗生素的风险和管理可能发生的不良反应提供方法。这是解决我们复杂的农业食品系统风险的重要工作，显然对消费者和农民都很重要。

Antimicrobial resistance (AMR) occurs because repeated exposure to antimicrobial drugs kills susceptible bacteria leaving the resistant types to multiply. Recent high-profile reports of the devastating consequences for human health caused by the resistance of disease-causing bacteria to antibiotics have emphasized the need to understand the processes that drive increasing prevalence of antimicrobial resistance in human and animal pathogens.Farm animals are considered to be a major source of AMR because of the large amounts of antibiotics used both to treat infection (therapeutic use) and to prevent infection (prophylactic use). However, little is known about the background levels of resistance in farming systems, even when animals are only treated with antibiotics when they need them (therapeutically). For instance, the sharing of genetic material by bacteria that are in close proximity is another route where AMR may emerge unexpectedly in otherwise non-related bacteria. AMR transmission between cattle is likely to be greater when they are close together, for example during the winter housed period. In this proposal we will use an experimental farm where cattle being raised for beef production only receive minimal antibiotic treatment described as 'best practice' by vets. We will monitor dynamics of AMR bacteria and genes in cattle dung in summer when the cattle are grazing in the field, and in the winter when they are housed together. We will carefully monitor cattle who have been sick and have been given antibiotics and those in the rest of the herd.The diet of farm animals may also effect increased AMR in their gut flora. Even common plants ('forage') like grass and clover that cattle commonly eat when they are out grazing produce natural antimicrobial compounds that may continue to be active in the stomach (rumen) where millions of bacteria thrive and multiply. In the winter, cattle are brought indoors and fed silage which is grassland plants that have been fermented to conserve them. Undigested diet and lots of bacteria from the rumen, and therefore perhaps AMR, are excreted in cow dung. We will analyse the dung of cattle that eat different forage types to find out if what they eat affects the likelihood of AMR arising in cattle fed one diet compared to another.Most cattle farming in the UK is situated in the hilly 'wet West' where the potential for rain to runoff fields into waterways is high. Recent increases in storms that cause lots of runoff and flooding may be due to climate change, are predicted to continue. At the same time, in recent years there has been an increasing recognition that AMR may arise in farm animals and be released from the farm environment to the natural environment in water and might therefore end up in drinking water, bathing water or in seafood. Normally, pollution from cattle dung in water is monitored using faecal indicator organisms (FIOs), which are bacteria that do not usually cause disease but which correlate with those that do (pathogens), and can be handled safely by scientists. It would be useful to know what proportion of FIOs carry AMR, because they are routinely tested for, facilitating estimates of AMR transmission to be estimated in the future. We will sample water flowing from fields that have been grazed by beef cattle or spread with their manure, and analyse the bacteria in the water including the FIOs to see if they are resistant to antibiotics.The results of this study should help us to understand whether AMR that arises in cattle herds may be transferred to the environment, whether management can limit AMR and its transport, and inform approaches for assessing risks of new antibiotics and managing adverse effects that might be occurring. It is important work for addressing risk in our complex agro-food system that is clearly important for both consumers and farmers.