Infection and Immunity

Antimicrobials are drugs used to treat bacterial infections. However, bacteria can acquire resistance against antimicrobials, which becomes a serious threat to public health. Often, resistance is acquired by the uptake of mobile genetic elements, that can quickly spread through different hosts and environments. Understanding how and why antimicrobial resistance is selected and spreads between animal and humans is of utmost importance.
The aim of the project is to assess whether the mobile gene pool configuration and the resistome in the gut microbiome of farm animals is shaped by feed produced in a circular economic system and feed additives. Furthermore, the transmission and gene flow network of antimicrobial resistant (AMR) genes in farm animals, humans and the environment will be determined. Next, we will define the rate at which mobile genetic elements (MGE’s) spread using in vitro systemsbetween humans and animals, across the food chain and in livestock farms.
Therefore, faecal samples from pigs and poultry, with or without feed additives, and humans in contact with these animals will be collected in collaboration with Cargill, UU-IRAS, WBVR and Vion. These samples will be analysed by different metagenome sequencing technologies, as short reads sequencing (Illumina platform), long read sequencing (Oxoford Nanopore) and ResCAP, which is a capture-based system for enrichment of AMR genes. Thus, the total non-host gene pool distributions, including the bacterial taxonomic distribution, the resistome, and the mobile gene pool in the gut of farm animals in relation to different feed ingredients and feed additives, such as essential oils and coccidiostatics, will be determined. Based on this first part of the project, transfer probabilities of selected MGE’s, such as plasmid, carrying antibiotic resistant genes, will be determined in the lab of Prof. Arjan de Visser (Wageningen University). To this end, identified key candidate donor and recipient bacterial species described above will be isolated and used in in vitro conjugation rate assays. Different fluorescent markers (BFP and YFP) will be introduced at neutral positions within the chromosomes of donor and recipient strains, and where possible in the resistance plasmids. Using newly developed models that detail the population dynamics during plasmid transfer, estimates of the plasmid transfer probability for each donor-recipient strain pair will be obtained, that take into account variation in conjugation opportunities. Finally, for a subset of strains, plasmid transfer rates will be quantified in a recently developed in vitro chicken gut model.

This project will give insights on the risks and contributions of livestock feeding regimes, feed additives and livestock production chains to the spread of mobile genetic elements carrying AMR genes at the animal-human-environment interface. Moreover, it will catalyse the development and implementation of novel effective approaches to prevent AMR emergence.

Contact
Matteo Buffoni