Understanding the role of host-pathogen interactions and the impact of management system on antimicrobial resistance in Brazilian livestock systems

巴西的牛肉产业规模巨大，是该国重要的外汇收入来源。巴西是世界上第二大牛肉生产国，拥有世界上最大的商业牛群，约有2亿头，来自180万个农场，从小型企业（每年<500头）商业化牛肉生产企业（每年超过4 000头）。大多数动物是在牧场上生产的，其中许多是在塞拉多（类似于稀树草原，巴西的一个重要生物群落）的低至中等肥力的土壤上生产的，<7%的屠宰动物是在饲养场生产的。尽管有这种广泛的牛肉生产系统，但抗菌剂的消费量很高。2010年，巴西在食用动物抗菌剂消费量方面排名世界第三，占全球农场动物抗菌剂消费总量的9%。农场动物对抗微生物剂的这种高消耗增加了宿主动物的微生物组（生活在动物肠道中的微生物种群）中产生抗微生物剂抗性（AMR）细菌的风险。有许多因素可能会促进宿主肠道中AMR细菌的增殖，该提议所基于的假设是宿主微生物组的变化可能会影响AMR细菌菌株的维持和流行。确定可能促进抑制AMR细菌的微生物组发展的干预措施，可以帮助控制巴西肉牛中AMR的发展和传播。我们假设，在巴西的牧场上完成的牛肉与在饲养场完成的牛肉相比，粪便AMR细菌的患病率较低，因为基于牧场的生产系统的强度较低。在巴西放牧的大部分牧场适合热带牧草的生长，或者在更集中管理的牧场中适合豆科植物的生长。热带牧草和豆科牧草都含有单宁，已知单宁具有抗微生物特性和抗生素抗性修饰特性。然而，单宁作为抗菌剂的功效和作用方式取决于它们的浓度和组成。本项目将研究单宁成分与摄入量之间的关系，以及这对宿主动物微生物组（以及对AMR细菌的敏感性）的影响。在该项目的第一阶段，我们将进行一项调查，以确定动物年龄（一岁和肥育动物）和生产系统（塞拉多放牧，更集中管理的牧场，饲养场）对巴西肉牛粪便样本中AMR细菌流行率的影响。我们还将确定动物肠道中微生物种群的组成（来自粪便样本），以研究是否存在与AMR细菌流行率较低相关的细菌种类模式。我们还将采集动物消耗的草料样本，并研究动物消耗的单宁的数量和组成是否可以解释其肠道微生物组的差异和AMR细菌的流行。这将使我们能够制定管理和饲养策略（将在项目的第二阶段进行研究），这可能会减少巴西肉牛中AMR细菌的流行，改善牛本身的健康状况，并提高肉类的安全性和可销售性。

The Brazilian beef industry is immense, and is a vital source of foreign revenue for the country. Brazil is the second largest producer of beef in the world, and has the world's largest commercial herd of approximately 200 million head produced on 1.8 million farms ranging from small enterprises (<500 head p.a.) to commercialised beef production enterprises (>4000 head p.a.). Most animals are produced on pasture, many of them on soils of low to medium fertility in the cerrado (similar to savannas, an important biome in Brazil) with <7% of slaughtered animals being produced on feedlots. Despite this extensive system of beef production, antimicrobial consumption is high. In 2010, Brazil was ranked third highest in the world for antimicrobial consumption by food producing animals, and accounted for 9% of total global farm animal antimicrobial consumption. This high consumption of antimicrobials by farm animals increases the risk of the development of antimicrobial resistant (AMR) bacteria in the host animal's microbiome (the microbial population living in the animal's gut). There are many factors which might encourage the proliferation of AMR bacteria in the host gut, and the hypothesis on which this proposal is based is that changes in the host microbiome may affect the maintenance and prevalence of AMR strains of bacteria. Identifying interventions that may then encourage the development of a microbiome that suppresses AMR bacteria could then help control the development and spread of AMR in Brazilian beef cattle. We hypothesise that beef finished on pasture in Brazil will have a lower prevalence of faecal AMR bacteria compared with those finished in feedlots, because of the less intensive nature of the pasture based production system. Much of the pasture grazed in Brazil is suitable either for the growth of tropical grasses or, in more intensively managed pastures, legumes. Both tropical grasses and forage legumes contain tannins, which are known to have antimicrobial properties and antibiotic resistance modifying properties. However, the efficacy and mode of action of tannins as antimicrobials depends on their concentration and composition. Elucidating the relationship between tannin composition and intake, and the effect this has on the host animal's microbiome (and susceptibility to AMR bacteria) will be investigated in this project. In the first stage of the project, we will conduct a survey to determine the effect of animal age (yearling and finishing animal) and production system (cerrado grazing, more intensively managed pasture, feedlot) on the prevalence of AMR bacteria in faecal samples taken from beef cattle in Brazil. We will also determine the composition of the microbial population in the animal's gut (from the faecal sample) to investigate whether there are patterns of bacterial species which are associated with a lower prevalence of AMR bacteria. We will also take samples of the forages consumed by the animal and investigate whether the amount and composition of tannin that the animal consumes can explain differences in its gut microbiome and the prevalence of AMR bacteria. This will then enable us to develop management and feeding strategies (that would be investigated in the second stage of the project) that might reduce the prevalence of AMR bacteria in Brazilian beef cattle, improving the health status of the cattle themselves and improving the safety and marketability of the meat.