Abstract
CRISPR-Cas immune systems are present in around half of bacterial genomes. Given the specificity and adaptability of this immune mechanism, it is perhaps surprising that they are not more widespread. Recent insights into the requirement for specific host factors for the function of some CRISPR-Cas subtypes, as well as the negative epistasis between CRISPR-Cas and other host genes, have shed light on potential reasons for the partial distribution of this immune strategy in bacteria. In this study, we examined how mutations in the bacterial mismatch repair system, which are frequently observed in natural and clinical isolates and cause elevated host mutation rates, influence the evolution of CRISPR-Cas–mediated immunity. We found that hosts with a high mutation rate very rarely evolved CRISPR-based immunity to phage compared to wild-type hosts. We explored the reason for this effect and found that the higher frequency at which surface mutants pre-exist in the mutator host background causes them to rapidly become the dominant phenotype under phage infection. These findings suggest that natural variation in bacterial mutation rates may, therefore, influence the distribution of CRISPR-Cas adaptive immune systems.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Highlights
In the face of infection by bacteriophages, bacteria have evolved a range of molecular mechanisms that provide immunity [1,2,3,4]
Despite the obvious benefits of CRISPR-mediated phage resistance when phages are present in the environment [8], the majority of bacterial genomes lack a CRISPR-Cas adaptive immune system [9,10,11,12,13], an estimate that undoubtedly is subject to sampling biases, as some clades of unculturable bacteria appear to be essentially devoid of CRISPR systems [14]
By comparing the evolution of phage resistance in WT PA14 and isogenic DmutS strains, we find that high mutation rates have a dramatic impact on the evolution of phage resistance, which changes from being almost exclusively CRISPR-based in the WT background to being almost exclusively surface-based in the DmutS background
Summary
In the face of infection by bacteriophages (phage), bacteria have evolved a range of molecular mechanisms that provide immunity [1,2,3,4]. IHF guides spacer integration to the correct promoter-proximal end of the CRISPR array, where spacers provide the highest levels of resistance to re-infection [43,44,45,46] Another example where an accessory host factor is essential for CRISPR functioning is in type II systems, which generally require RNase III for processing of the pre-CRISPR RNA transcript into short CRISPR RNA molecules (crRNA) that guide Cas complexes to target and destroy foreign elements [47,48,49]. These data help us to understand how natural variation in mutation rates may impact the phylogenetic distribution of CRISPR-Cas systems, and have implications for phage therapy applications, where they may help to predict the relative importance of CRISPR- and surface-based resistances on the basis of the bacterial mutation rate
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Schedule a callMore From: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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