Overcoming hurdles to translate phage research

Lead Research Organisation: University of Leicester
Department Name: Genetics

Abstract

Antimicrobial resistance (AMR) is an increasing global health threat. In 2019, 4.95 million deaths were associated with bacterial AMR infections and annual death tolls worldwide are predicted to reach 10 million by 2050 unless interventions are taken. AMR in clinical settings is linked to antimicrobial use in animal production, where 70% of total antimicrobials manufactured are used. This is evidenced by high AMR levels in bacterial pathogens such as Salmonella which cause disease in livestock and foodborne illness in humans. Globally, Salmonella causes 93 million human infections every year, with poultry and swine being the main foodborne reservoirs, at 48% and 27% respectively. Salmonella infections are becoming increasingly resistant to antibiotics, and alternative treatments are urgently needed for animal infections in order to improve animal welfare, produce healthy food and prevent foodborne transmission. We have been developing bacteriophages (phages) as a new treatment and in this grant will carry out the work necessary to translate our laboratory and experimental trial work into products that can be developed for widespread agricultural use.

Phages are natural viruses that specifically kill bacteria. They are highly specific to bacteria, only affecting their targeted bacterial species so they can be developed as new medicines that maintain a healthy microbiome whilst treating disease. Phages have been identified by many, including the UK government and the World Health Organisation as having great potential to prevent and treat infections. We have robust data on the use of phages to treat Salmonella in poultry and swine in experimental settings. To translate this work to the widespread usage it is necessary to establish how to use phages most effectively, produce products at scale and how to effectively regulate their use.

The phage product we developed effectively kills the Salmonella strains that are commonly associated with poultry and swine, including those which are multi-drug resistant. This would benefit human and animal health, and improve food security and productivity. Our product uses two phages; SPFM10 and SPFM14. We showed that this combination effectively kills strains from the most prevalent UK Salmonella subgroups that cause infection in poultry and swine; in vitro and in vivo, and improves animal health and their productivity. To translate this to commercial veterinary products requires knowledge of parameters needed to scale up phage production. It also needs data on the optimal phage dosage, on all safety aspects of the final product and a clarification of regulatory pathways. Work resulting from this grant will overcome these barriers, and provide the foundation for our research to achieve commercial, economic and societal benefits.

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