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

• Published in: Nature communications Vol. 9; no. 1; p. 61
• Main Authors: Goldberg, Gregory W., McMillan, Elizabeth A., Varble, Andrew, Modell, Joshua W., Samai, Poulami, Jiang, Wenyan, Marraffini, Luciano A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.01.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 45/70; 45/77; 631/1647/1513/1967/3196; 631/326/1321; 631/326/4041; 631/326/421; Bacteriophages; CRISPR; CRISPR-Cas Systems - genetics; Deoxyribonucleic acid; DNA; Fitness; Humanities and Social Sciences; Immunity; Immunological tolerance; Infections; Lysogens; Lysogeny - genetics; multidisciplinary; Nuclease; Parasites; Phages; Populations; Prophages; Reproductive fitness; Ribonucleic acid; RNA; RNA phages; Science; Science (multidisciplinary); Spacer; Staphylococcus aureus - genetics; Staphylococcus epidermidis - genetics; Transcription; Virus Diseases - genetics
• ISSN: 2041-1723; 2041-1723
• 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. CRISPR-Cas systems, such as type III-A CRISPR-Cas, provide an immune mechanism for prokaryotic hosts to resist parasites, including phages. Here, the authors show that maintenance of conditionally tolerant type III-A systems can affect the fitness of Staphylococcus aureus lysogens.