Different genetic and morphological outcomes for phages targeted by single or multiple CRISPR-Cas spacers.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
The Royal Society
MetadataShow full item record
Watson, B., Easingwood, R., Tong, B., Wolf, M., Salmond, G., Staals, R., Bostina, M., & et al. (2019). Different genetic and morphological outcomes for phages targeted by single or multiple CRISPR-Cas spacers.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 374 (1772), 20180090. https://doi.org/10.1098/rstb.2018.0090
CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against genetic invaders, such as bacteriophages. The systems integrate short sequences from the phage genome into the bacterial CRISPR array. These ‘spacers’ provide sequence-specific immunity but drive natural selection of evolved phage mutants that escape CRISPR-Cas defence. Spacer acquisition occurs by either naïve or primed adaptation. Naïve adaptation typically results in the incorporation of a single spacer. In contrast, priming is a positive feedback loop that often results in acquisition of multiple spacers, which occurs when a preexisting spacer matches the invading phage. We predicted that single and multiple spacers, representative of naïve and primed adaptation respectively, would cause differing outcomes after phage infection. We investigated the response of two phages, ɸTE and ɸM1, to the Pectobacterium atrosepticum type I-F CRISPR-Cas system and observed that escape from single spacers typically occurred via point mutations. Alternatively, phages escaped multiple spacers through deletions, which can occur in genes encoding structural proteins. Cryo-EM analysis of the ɸTE structure revealed shortened tails in escape mutants with tape measure protein deletions. We conclude that CRISPR-Cas systems can drive phage genetic diversity, altering morphology and fitness, through selective pressures arising from naïve and primed acquisition events.
Pectobacterium, Bacteriophages, Point Mutation, CRISPR-Cas Systems
External DOI: https://doi.org/10.1098/rstb.2018.0090
This record's URL: https://www.repository.cam.ac.uk/handle/1810/289643