Know your enemy: systematic discovery of Salmonella anti-Phage Defences for the improved design of phage therapeutics

Antimicrobial drug resistance is a serious global threat that make us to fear the return of the mortality rates from pre-penicillin times. A promising alternative to antibiotic drugs is the phage therapy, which is based in viruses that kill bacteria. The rational design of effective phage therapeutics requires a fundamental understanding of evolutionary co-adaptation of phages and bacteria. These co-adaptations have led to the development of multiple anti-phage defence systems in bacteria which modulate their susceptibility to be killed by phages at strain level. In this way, the study of the diversity and mechanisms of action of defence islands in bacterial pathogens represents crucial knowledge for improving rapid delivery of phage-based therapeutics. The proposed work aims to deeply characterize the anti-phage defences in a human pathogen, Salmonella, to provide the strategy to discover and classify phage counter-defences for an optimal design of phage therapy. This project will characterize the genetics population of Salmonella to study the distribution and diversity of anti-phage defence islands and will validate the activity and function of the defence and counter-defence in bacteria and phage, respectively. The experienced researcher (ER) will establish a collaborative link between the laboratories of laboratories of Dr. German Bou (Spain), who has extensive experience in clinical microbiology and genetic modification methods, and Prof. Martin Polz (USA), who is a world expert in the ecology and evolution of environmental microbiology. This collaboration will allow to perform the most advanced methods in population and comparative genomics, isolation and discovery of phages, large scale phage host range assays and genetic modification of bacteria. The data generated in this project will be essential to understand the anti-phage defence mechanisms and to improve clinical decisions to maximize the efficacy of phage therapeutics.