ProSAR · Role of prophages in the evolution and spread of antiviral resistance in Pseudomonas aeruginosa

Most bacteria carry chromosomally integrated viral mobile genetic elements – prophages. Although parasitic, prophages can benefit their host via genes with systems to defend the host from infection by other phages. How does conflict between these phages shape the evolution and the spread of the defensive genes?I aim to study how prophage-mediated anti-viral defence spreads through populations of the pathogen Pseudomonas aeruginosa. Preliminary data shows that prophages can provide hosts with different profiles of resistance against virulent (non-integrating) phages. I will first identify the genetic bases of these defences and how they act, then establish a novel multiplexed fluorescence-based system to follow the vertical selection and horizontal transmission of defensive prophages, in the presence of virulent phages. This dynamic system will provide the basis for establishing, in collaboration, a more generalisable mathematical model of prophage spread in bacterial population. Finally, I will use evolution experiments to determine if and how virulent phages can mutate to escape this resistance. This project will advance our knowledge as to what extend the myriads of prophages residing in bacterial genomes may alter phage resistance phenotypes of their hosts and drive the horizontal propagation of defensive genes to new hosts. This study is pertinent to clinical applications of phages as the spread of prophage-encoded defence systems could undermine the outcomes of phage-based therapies.This multidisciplinary project integrates my expertise in genetic engineering and experimental evolution with that of the host lab in phage molecular biology and ecology. A strong dissemination and communication plan will ensure relevant stakeholders – policy makers, clinicians, and scientific audiences – have access to key findings. Working within the CNRS gives me access to high quality equipment, collaborations and training to propel my career as an independent research.