Cleavage of viral DNA by restriction endonucleases stimulates the type II CRISPR-Cas immune response

Fitness costs of CRISPR-Cas systems in bacteria

“…RM system restriction endonucleases can provide a short-term defence against phage infection, that may be rapidly overcome via phage genome methylation. However, it is possible that this initial restriction can enable CRISPR arrays to acquire spacer sequences from the cleavage site, which can then provide a secondary level of immunity against the methylated phage via CRISPR-Cas activity [37]. Interestingly, this sequential mechanism of activity provides a conceptual parallel to more complex eukaryotic immunity, where the innate response provides an initial line of defence and activates a second and more robust adaptive response [37].…”

“…While co-occurrence could be indicative of co-transfer in ‘defence islands’, here they were shown to be rarely associated with proximity co-localization in the genome [31], further supportive of the provision of additive functionality [31, 32] and the conditions selecting for one also being positively selective for others. Mechanistic insights into the relationship between CRISPR-Cas and RM systems have been described in high resolution in Staphylococcus [37]. RM system restriction endonucleases can provide a short-term defence against phage infection, that may be rapidly overcome via phage genome methylation.…”

“…It is interesting to consider the difference in selection dynamics with CRISPR-Cas between a mechanism that prevents phage entry into the cell (mutation of surface receptors) [38] and a mechanism that functions upon phage entry (RM systems) [37]. Where receptor mutation may remove the fitness benefit of CRISPR-Cas immunity in a population [38], RM systems are observed to co-occur across genomes with CRISPR-Cas [31] and can function in an additive manner [37]. Furthermore, CRISPR immunity may be associated with an infection-dependant cost [44], which has been attributed to toxicity caused by phage gene expression prior to cleavage by CRISPR-Cas [45].…”

“…Exploration of this should aim to link fundamental mechanistic work with natural populations. For example, it would be interesting to investigate the prevalence of the two-step additive immunity mechanism of RM systems and CRISPR-Cas systems described in Staphylococcus aureus across different bacterial families [37]. And going in the other direction, given that genome co-occurrence suggests additive functionality for other putative defence systems [e.g.…”

PADLOC: a web server for the identification of antiviral defence systems in microbial genomes

“…In addition, our broad taxonomic analyses revealed notable differences in the diversity and abundance of defence systems in many taxa, raising the question of what factors drive the requirement for more defence against phages, and whether differences are driven by ecological factors such as phage diversity and encounter rates (reviewed in 92 ). Recent studies have also identified interplay between defence systems, with synergistic or antagonistic effects ( 42 , 93 , 94 ) and as more types of defence systems are discovered, our understanding of compatibility between systems needs to be revisited. The PADLOC web server provides a convenient and accessible platform to detect suitable candidate strains for experimental work to resolve these outstanding questions.…”