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

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.

Food security and AMR are strategic priorities for BBSRC and FAPESP. The proposed research will provide an improved understanding of the diversity, drivers, evolution and spread of AMR in Salmonella and will provide an evidence base for future interventions in the Brazilian food chain. These data are particularly relevant, given the importance of pigs and poultry to the Brazilian economy and the projected doubling of antimicrobial usage in these systems by 2030 - identifying the role of AMR will allow suitable control strategies to be applied most effectively. Beneficiaries will include policy makers, industry, and the public. The work proposed here will also develop further bioinformatics capacity within Brazil by providing additional training in these skills. The training will focus on open source pipelines and tools so that these methods can be easily adopted in the Brazilian laboratories.

Policy makers: AMR and Salmonella in the food chain is a concern for many governmental agencies, including the Food Standards Agency (FSA) in the UK and the Department of Agriculture in Brazil. We will have strong engagement with these agencies throughout the project; Dr Mather is an FSA Fellow and meets regularly with the organisation where discussion of the project can occur. Quadram Institute Bioscience (QIB) also has long-standing collaborative links with the Animal and Plant Health Agency and Public Health England, which will ensure dissemination of our results to relevant agencies. Drs Moreno and Knöbl have links with state government official laboratories as such as the Biological Institute and Butanta Institute.

Industry: Drs Moreno and Knöbl have worked with the pig and poultry industries, respectively, in Brazil for many years. Their close collaborations will facilitate communication with the relevant stakeholders. QIB also has many links with the pig and poultry industries in the UK; engagement with these industries in both countries over the course of the project will facilitate genuine impact of this work.

Public: Accessible summaries of our research in lay terms will be published on the websites of our respective institutions, University of São Paulo and Quadram Institute Bioscience, and shared via social media. We will also participate in various public engagement events, such as the Norwich Science Festival. The impact will be an improved understanding of what antimicrobial resistance is and how it emerges and spreads.

Training and knowledge exchange: Throughout the course of this work, training and up-skilling in bioinformatics, sequencing and epidemiology will be provided for both the Brazilian and UK researchers associated with this project, particularly developing further the bioinformatics capacity in Brazil.