Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts

Nat Commun. 2018 Jan 4;9(1):61. doi: 10.1038/s41467-017-02557-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophages*
  • CRISPR-Cas Systems / genetics*
  • Lysogeny / genetics*
  • Prophages*
  • Staphylococcus aureus / genetics*
  • Staphylococcus epidermidis / genetics*
  • Virus Diseases / genetics*