During this project I have set up a new collaboration with Prof. Gandon, CNRS France. This collaboration aimed at understanding the effect of host heterogeneity on evolutionary emergence of parasites, and together with colleagues I used the P. aeruginosa – phage as a model system to study predictions from theoretical models build by Prof. Gandon. This manuscript is currently in preparation, expected submission April 2018.
In addition, I have set up an entirely new model system in the lab to study CRISPR evolution and the interactions with phages and other MGEs. For this, I set up the Streptococcus thermophilus system, which showed high levels of CRISPR evolution (i.e. acquisition of spacers) upon phage infection. However, I observed that spacer diversity was much lower than what I typically observed with the P. aeruginosa system, and frequently phage was not driven extinct. I therefore pursued further experiments with this system to study the co-evolutionary dynamics, which is still ongoing. The data so far indicate that in S. thermophilus bacteria co-evolve with a dynamics that most closely resembles an arms race, while their phages co-evolve according to either arms race or fluctuating selection dynamics. I am now performing molecular typing of these clones as well by deep sequencing of phage and host genomes to genetically underpin these observations. I expect to submit a manuscript on this around June 2018.
During this fellowship I have also obtained follow-up funding to start my own independent research line aimed at understanding how CRISPR-Cas interacts with MGE, in particular plasmids. I will use this project to understand how CRISPR-cas can be used to remove antimicrobial resistance plasmids from bacterial communities.
Overall, the scientific outcomes of this project and the progress made beyond the state of the art have important implications for society. The knowledge generated during this project is important for understanding the risks, potential and consequences of phage therapy for the treatment of bacterial infections as an alternative to the use of antibiotics. In addition it is important for the optimal use of CRISPR-Cas in dairy industry to protect bacterial starter cultures (e.g. for production of yoghurt and cheese) against lethal phage infections. Furthermore, this project has paved the way towards further funding aimed at understanding whether CRISPR-Cas can be used to remove antimicrobial resistance, which is one of the biggest threats to our health of our time.
