Epidemiological analysis of antimicrobial resistance in the food chain in the metagenomics era: from antimicrobial resistant pathogens to the faecal resistome of humans and livestock

Abstract

As a consequence of human and animal antimicrobial use (AMU), antimicrobial resistance (AMR) has emerged. Antimicrobial resistant bacteria – containing antimicrobial resistance genes (ARGs) – are ubiquitous in our living environment. Not only can humans be directly exposed to AMR bacteria in livestock, livestock bacteria could potentially also serve as a reservoir for horizontal gene transfer through which human pathogenic bacteria can acquire ARGs. Studies investigating determinants for livestock and human AMR carriage should therefore also include the study of ARGs to enable the estimation of the overall exposure of humans to – and the risk posed by – AMR. This thesis concerns the epidemiological analysis of AMR in the European food chain. It describes how AMU and AMR in livestock affect AMR in humans and focuses on identifying determinants for AMR at the genomic level. It elaborates on how the pig and poultry gut resistome, i.e. the full collection of ARGs in the gut, is affected by AMU, livestock farm management and on-farm biosecurity practices. Molecular techniques like qPCR and next-generation sequencing techniques (i.e. metagenomic sequencing) are applied to identify an umbrella of on-farm AMR mitigation measures targeted at the livestock resistome, while generating data regarding the genetic characteristics of resistance. This work also analyses AMR in, and the faecal resistome and bacteriome of, persons occupationally exposed to AMR in livestock (i.e. farmers and slaughterhouse workers), who might not only be highly exposed but also serve as entry points for the spread of AMR bacteria and ARGs to the general population. Finally, the strengths and limitations of the application of metagenomic methods within AMR surveillance networks are discussed. A more detailed summary can be found in the addendum to this thesis (page 256, in English and Dutch)