Mechanism of multiple drug resistance and genetic evolution of prevalent Salmonella serotypes derived from animals

Background: Despite the growing body of research around antimicrobial resistance (AMR) within industrial farming systems and in meat, there is a knowledge gap in our understanding of the origin and evolution of an important 'food poisoning' organism - Salmonella - which is the cause of non-typhoidal gastrointestinal infections in humans and a likely driver of multiple drug resistance (MDR).

Salmonella remains the leading cause of infectious gastroenteritis, causing approximately 93 million infections and 155,000 deaths worldwide each year, mainly by consumption of contaminated foods of animal origin, particularly poultry and pork products [Castro-Vargas et al. 2020, Shen et al., 2022] .

Salmonella infections in humans are mainly caused by two virulent serotypes, S. Enteritidis and S.

Typhimurium [Sedrakyan et al., 2022] which are common in broilers and pigs globally and shows high resistance to commonly used antibiotics in poultry and pork production [Lenchenko et al., 2020, Monte et al., 2019].

Despite the pressing nature of this issue, there are still research gaps in our understanding of the mechanisms of acquisition of MDR Salmonella in the food supply chain and the lack of understanding of the complex pathways by which AMR can spread within and between animals, people, and the environment how these organisms have evolved to occupy the ecology of the 'farm to fork' pathway.

Aims: This project aims to investigate the factors influencing the generation and evolution of Salmonella which allows persistence in the supply chain and understand whether these adaptions could inform the challenge of effective interventions (such as phage treatments) to reduce the use of antimicrobials in food animal production and limit the spread of AMR.

Methodology: We will conduct multidisciplinary studies throughout the poultry/pork supply chain focussing on intensively reared chicken and pigs 'from farm to fork'.

We will use the latest approaches in traditional and molecular investigations to unravel the acquisition and carriage of MDR Salmonella in food animal supply chains.

The UK team will continue their current pilot investigation - with a major UK processor funded by the Food Standards Agency (FSA) on the extent of MDR bacteria during the processing of chicken.

The collaboration with China will significantly extend the FSA study by tracking batches of chicken/pigs from farms (animal feed and waste), and natural water catchments used in slaughter processes and processing facilities with a range of environmental sampling from likely 'hot spot' areas especially where biofilms may be present.

Parallel work will investigate a panel of Salmonella phages and their host strains for the evolution of resistance development and the impact of this evolution on resistance /sensitivity to antimicrobials.

Results: Salmonella isolates obtained in this one health context from China and the UK will be intensely investigated using detailed comparative genomics building a significant collection of new isolates from both countries for full genetic characterisation.

Outcomes: This genomic data together with laboratory studies addressing key mechanisms utilising a panel of specific phages for the evolution of resistance development and the impact of this evolution on resistance sensitivity to antimicrobials in order to design mitigating strategies for reducing and eliminating persistence and epidemics of MDR Salmonella as part of our fight against the spread of antibiotic resistance.

This project will make a positive contribution to the present and future action plans for AMR by furthering our understanding of how 'one health' AMR spreads through the chicken/pork farm to fork environment and solutions to these challenges will be of global importance.