Drivers and dynamics of antimicrobial resistance and Salmonella in Brazilian pig and poultry production

在牲畜中发现的细菌的抗微生物药物耐药性对动物和人类的健康构成严重威胁；牲畜中的耐药感染也有重大的经济影响。肠沙门氏菌是猪和家禽中最重要的细菌病原体之一，被认为是人类感染的两个主要宿主。巴西是世界上最大的猪肉和鸡肉生产国和出口国之一，这些行业是该国经济的重要贡献者。在过去10-15年中，这些生产系统发生了变化，包括在家禽中大规模强化和引入肠炎沙门氏菌疫苗，导致巴西从猪和家禽中观察到的沙门氏菌血清型流行率发生了巨大变化。这些变化可能是由抗菌素使用和耐药性驱动的，但这一问题尚未得到充分调查。我们提案中概述的研究建立在我们为期一年的资助基础上，该资助旨在调查过去10年来从巴西猪和家禽中分离的沙门氏菌中AMR决定因素的多样性和进化。在我们的工作过程中，我们将大幅增加巴西家畜沙门氏菌基因组序列的数量；通过这样做，我们可以确定它们在全球范围内的位置，并确定在巴西出现特定亚型的时间。我们还将研究基因决定因素，如抗菌素耐药性，促进沙门氏菌在食物链中持续存在。通过调查牲畜生命过程中抗菌素耐药性和血清型的变化，我们将有助于为潜在的疫苗策略提供信息。最后，通过检测家畜肠道共同非致病菌的AMR，并将总耐药性与抗菌药物的使用联系起来，我们将确定它们作为致病菌（如沙门氏菌）AMR基因储存库的潜在作用，因为AMR基因可以通过水平基因转移在细菌之间移动。我们将利用全基因组测序、最先进的长读测序，结合分子生物学和流行病学来实现这些目标。该提案利用了英国Quadram生物科学研究所（QIB）的Alison Mather博士和Justin O'Grady博士与圣保罗大学（USP）的Andrea Moreno博士、Terezinha博士Knöbl和Luisa Moreno博士以及QIB的合作者Emma Doughty博士和动植物卫生机构的Liljana Petrovska博士之间的有效和富有成效的合作。到2030年，巴西家畜抗菌素消费量预计将增加近一倍；这项研究将解决AMR对巴西牲畜物种造成的巨大健康和经济威胁，这将有助于确定在哪些地方可以最有效地应用适当的控制策略。

Antimicrobial resistance (AMR) of bacteria found in livestock represent a grave threat to the health of both animals and humans; resistant infections in livestock also have a significant economic impact. Salmonella enterica is one of the most important bacterial pathogens in pigs and poultry, which are thought to be two of the major reservoirs for human infections. Brazil is one of the world's largest producers and exporters of pig and chicken meat, and these industries are significant contributors to the country's economy. Change in these production systems over the last 10-15 years, including massive intensification and introduction of a Salmonella Enteritidis vaccine in poultry, have led to dramatic shifts in the Salmonella serotype prevalence observed from pigs and poultry in Brazil. These shifts are probably driven by antimicrobial use and resistance, but this issue has not been fully investigated.The research outlined in our proposal builds on our one-year pump-priming grant investigating the diversity and evolution of AMR determinants in Salmonella isolated from Brazilian pigs and poultry over the last 10 years. In the course of our work, we will dramatically increase the number of available Salmonella genome sequences from Brazilian livestock; by doing so, we can identify where they fit in the global context and identify when specific subtypes emerged in Brazil. We will also look at the genetic determinants, such as AMR, facilitating the persistence of Salmonella through the food chain. By investigating the changes in AMR and serotype over the life course of livestock animals, we will help inform potential vaccine strategies. Finally, by examining AMR in the gut co-resident non-pathogenic bacteria in livestock and correlating total resistance with antimicrobial usage, we will ascertain their potential role as a reservoir of AMR genes for pathogenic bacteria such as Salmonella, as AMR genes can move between bacteria through horizontal gene transfer. We will achieve these aims using whole genome sequencing, state-of-the-art long read sequencing, combined with molecular biology and epidemiology. This proposal exploits the effective and productive collaboration between Dr Alison Mather and Dr Justin O'Grady at Quadram Institute Bioscience (QIB) in the UK, and Dr Andrea Moreno, Dr Terezinha Knöbl and Dr Luisa Moreno at the University of São Paulo (USP), along with collaborators Dr Emma Doughty at QIB and Dr Liljana Petrovska at the Animal and Plant Health Agency. Antimicrobial consumption in livestock is expected to nearly double in Brazil by 2030; this research will tackle the huge health and economic threat posed by AMR to Brazilian livestock species, which will help identify where suitable control strategies could be applied most effectively.