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

Gregory W. Goldberg, Elizabeth A. McMillan, Andrew Varble, Joshua W. Modell, Poulami Samai, Wenyan Jiang and Luciano A. Marraffini ()
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Gregory W. Goldberg: The Rockefeller University
Elizabeth A. McMillan: The Rockefeller University
Andrew Varble: The Rockefeller University
Joshua W. Modell: The Rockefeller University
Poulami Samai: The Rockefeller University
Wenyan Jiang: The Rockefeller University
Luciano A. Marraffini: The Rockefeller University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02557-2

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