The impact of temperature on host-parasite interactions and co-evolution

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Antimicrobial resistance is a growing global threat because of widespread antibiotic overuse in medicine and agriculture. This has prompted investigations into alternative methods for the treatment of bacterial infections. A promising candidate is bacteriophages (phages), viruses which target and kill bacterial pathogens. While the ability of phages to repress bacteria has been demonstrated under both lab conditions and in clinical trials, phage studies have generally neglected the impact of environment stresses, including variation in temperature, on bacteria-phage interactions. Phage therapies are expected to experience broad temperature ranges both within mammalian hosts (normal body temperature vs infection-induced fevers) and between hosts (humans vs assorted livestock). However, it is unclear whether phage activity is maintained, promoted, or restricted across temperatures. The overall goal of this project is to investigate how temperature mediates interactions between bacteria and phage. Specifically, this project aims to i) investigate the impact of temperature on phage activity; ii) determine whether phages can be evolved experimentally to improve their activity across temperatures; and iii) assess the impact of temperature on co-evolution between bacteria and phages. Using the opportunistic pathogen Pseudomonas aeruginosa and a diversity of lytic phages, this project will improve our understanding of how variation in body temperature both within and between mammalian hosts affects phage treatments or bacteria-phage interactions naturally within the microbiome. Further, it will determine whether changes in temperatures restrict or facilitate the evolution of bacterial resistance to phage. The findings of this project will have important implications for the selection and application of phages to treat bacterial infections.Given the relevance of this project both in tackling antibiotic resistance, treating bacterial infections, and assessing the potential impact of changes in body temperature on the human "phageome", the BBSRC priorities addressed include:1. Combatting antimicrobial resistance2. Animal health3. Integrative microbiome research