A Comparative One-Health Approach tackling AMR infections UK and Indian Livestock

Antimicrobial resistance (AMR) is one of the greatest global challenges we face this century. Recent estimates suggest almost 5 million deaths were linked to AMR infections worldwide in 2019. Antimicrobials are used as "growth promoters" in livestock throughout the world, although this is banned in the UK. Using antimicrobials routinely like this allows bacteria which carry antimicrobial resistance genes (ARG) to survive and grow in the guts of livestock. These ARG can transfer between bacteria and may spread to disease-causing pathogens, making these diseases increasingly difficult to treat. These pathogens can transfer to humans through direct contact, or consumption of contaminated food. This is a problem, even in the UK which banned antibiotic growth promoters, as AMR pathogens can spread between countries by international travel, trade, and migratory wildlife. Much is unknown about how ARG spread between animals, humans, and the environment and this needs to be understood before we can design effective interventions. Combatting AMR requires a global approach to reduce overall antimicrobial use in animals and humans and the pursuit of alternative treatments.

In this project, researchers from the UK and India will study the spread of AMR in dairy farms in the UK and Central India. Our focus is the bacterium E. coli which causes a range of infections in animals and humans. E. coli is a critical priority for control by the World Health Organization (WHO) because it causes infections that are increasingly multi-drug resistant, and it can survive in the environment for extended periods. We will track the spread of ARG and E. coli in the environments of five dairy farms in India, and two in the UK, over two year period. We are focussing on dairy cattle because they are susceptible to diarrhoea caused by E. coli, particularly when young; and are frequently treated with antimicrobials to control other infections such as mastitis. India is also the largest producer of milk in the world, much of which is consumed raw within the country; so there is a high risk of foodborne infection in humans.
We will take samples of faeces from livestock every two months and farm workers every four months, as well as environmental samples such as rodent and bird faeces, milk samples and swabs from equipment and machinery. These samples will be cultured to detect E. coli, and these bacteria will then be screened to determine their resistance to a panel of antibiotics. We will also use DNA sequencing of all cattle and human faecal samples to determine ARG carried by other microbes. Data on antibiotic use and practices will be gathered for each farm using questionnaires and interviews. This will help us to determine whether changes that we see in E. coli or AMR patterns over time can be linked with antimicrobial use or farm management.

Lastly, we will develop an alternative to antibiotic treatment of livestock, using viruses called bacteriophage or 'phage'. These phage only infect a specific subset of bacteria, e.g. coliphages which infect E. coli. We have an existing collection of coliphages, and a panel of pathogenic E. coli strains isolated from livestock in the UK, EU and elsewhere over the past 30 years. We will isolate new coliphages from faecal and wastewater samples in the UK and India and screen these against our panel of E. coli strains, plus any more that we isolate from our two-year dairy farm study. This will be done using high-throughput equipment capable of processing up to 5,000 combinations of phage and bacteria at once. The data from these experiments will be used to develop mathematical models or "machine learning algorithms" that can analyse patterns in data to select the best phage candidates to use to control the pathogenic E. coli in livestock. At the end of the project, we will work with industrial partners to further develop this new treatment into a viable therapeutic alternative to antibiotics.