Abstract
CRISPR–Cas systems offer an immune mechanism through which prokaryotic hosts can acquire heritable resistance to genetic parasites, including temperate phages. Co-transcriptional DNA and RNA targeting by type III-A CRISPR–Cas systems restricts temperate phage lytic infections while allowing lysogenic infections to be tolerated under conditions where the prophage targets are transcriptionally repressed. However, long-term consequences of this phenomenon have not been explored. Here we show that maintenance of conditionally tolerant type III-A systems can produce fitness costs within populations of Staphylococcus aureus lysogens. The fitness costs depend on the activity of prophage-internal promoters and type III-A Cas nucleases implicated in targeting, can be more severe in double lysogens, and are alleviated by spacer-target mismatches which do not abrogate immunity during the lytic cycle. These findings suggest that persistence of type III-A systems that target endogenous prophages could be enhanced by spacer-target mismatches, particularly among populations that are prone to polylysogenization.
Highlights
CRISPR–Cas systems offer an immune mechanism through which prokaryotic hosts can acquire heritable resistance to genetic parasites, including temperate phages
Given that mobile genetic elements (MGEs) can facilitate the spread of beneficial genes within prokaryotic populations, it was proposed that resistance to foreign DNA elements by CRISPR–Cas systems could jeopardize the survival of bacteria which rely heavily on MGE-mediated horizontal gene transfer (HGT)[4], and in turn promote the evolution of strains that do not harbor CRISPR–Cas systems[15,16]
Toxic chromosomal targeting may result from CRISPR–Cas immunity directed at temperate phages which integrate into the host chromosome as prophage DNA during lysogenic infections[28,29]
Summary
CRISPR–Cas systems offer an immune mechanism through which prokaryotic hosts can acquire heritable resistance to genetic parasites, including temperate phages. The type III-A system of S. epidermidis RP62a was further shown to encode a targeting complex with nucleases that license cleavage of RNA in addition to DNA13, as well as an auxiliary RNase (Csm6) that can assist in the degradation of phage transcripts during lytic infection[35]. These type III-A nucleases allow the system to prevent temperate phage propagation when its targets are transcribed during lytic infection or prophage induction, and yet tolerate prophages while their targets are sufficiently repressed in the chromosome
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