Ecological and Evolutionary framework for the design of novel bacteriophage therapy products
Lead Research Organisation:
University of Oxford
Department Name: Biology
Abstract
The healthcare system is increasingly under pressure due to the rise of antimicrobial resistance in bacterial pathogens. Multiple call to arms have resulted in a diversification of strategies to mitigate this issue. Human phage therapy is currently a widely advocated "post-antibiotic" approach in which we use the viruses of bacteria, or phages, to clear bacterial infections. It offers multiple advantages,including i) a high targeting specificity, with phages typically infecting only specific strains within a bacterial species, ii) self-dosing through amplification in situ, and iii) co-evolution of the phages with their host, so that if a bacterial strain becomes resistant to aphage, we can find new phage variants that will be able to infect it.
In this proposal, we address two current limitations of phage therapy: the first concerns methods for phage discovery, a task that hasproved challenging in some pathogens. Indeed, isolating virulent phages from the environment to infect specific strains from patients appears at times impossible. We propose here to weaponize the abundant prophages found in bacterial chromosomes using anexperimental evolution approach. The second limitation concerns the combination of phages into cocktails that can be broadly effective to target specific pathogens. For this task, we will implement Biodiversity-Ecosystem functioning strategies to discover design rules for optimized phage combinations. We have chosen to implement our approach on the clinically relevant bacteria: Pseudomonas aeruginosa.
This project will be performed in synergy with a lab that has considerable expertise in evolutionary microbiology and ecology, and where I can bring my own expertise of phage microbiology and large-scale omics data analysis. We believe this topic is timely and of high relevance for the EU and beyond as we work to further unleash the potential of phage therapy for human health and limit the cost of antimicrobial resistance in our societies.
In this proposal, we address two current limitations of phage therapy: the first concerns methods for phage discovery, a task that hasproved challenging in some pathogens. Indeed, isolating virulent phages from the environment to infect specific strains from patients appears at times impossible. We propose here to weaponize the abundant prophages found in bacterial chromosomes using anexperimental evolution approach. The second limitation concerns the combination of phages into cocktails that can be broadly effective to target specific pathogens. For this task, we will implement Biodiversity-Ecosystem functioning strategies to discover design rules for optimized phage combinations. We have chosen to implement our approach on the clinically relevant bacteria: Pseudomonas aeruginosa.
This project will be performed in synergy with a lab that has considerable expertise in evolutionary microbiology and ecology, and where I can bring my own expertise of phage microbiology and large-scale omics data analysis. We believe this topic is timely and of high relevance for the EU and beyond as we work to further unleash the potential of phage therapy for human health and limit the cost of antimicrobial resistance in our societies.
