The paradoxical relationship between CRISPR-Cas and phage susceptibility in Pseudomonas aeruginosa

CRISPR-Cas systems are part of the pan-immune system of Pseudomonas aeruginosa and have been shown to limit horizontal gene transfers in that species. Indeed, isolates equipped with these systems tend to have smaller genomes and CRISPR spacers targeting integrative conjugative elements, phages, and plasmids. In this work, we investigate the genomic effects and phenotypic consequences of CRISPR-Cas systems in P. aeruginosa. First, we establish that the population structure is a confounding factor of the relation between genome sizes and the presence of CRISPR-Cas systems in P. aeruginosa as isolates from group II are, on average, 200 kbp larger than those from group I, and have a lower likelihood of possessing CRISPR-Cas systems. Second, we show that the impact on the genome size of CRISPR deactivation by anti-CRISPR proteins differs between the various CRISPR-Cas types found in this species (I-C, I-E, and I-F). Finally, we highlight a paradoxical, positive correlation between the presence of CRISPR-Cas systems and the chances of the host being infected by a set of distinct, strictly virulent Pseudomonas phages. We propose that this increased phage susceptibility in the presence of CRISPR-Cas is linked to a depletion of other accessory defense system genes in isolates with CRISPR-Cas systems. Note: This manuscript was published as a chapter in the doctoral dissertation of Cedric Lood [72]