TY - JOUR
T1 - Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
AU - Goldberg, Gregory W.
AU - McMillan, Elizabeth A.
AU - Varble, Andrew
AU - Modell, Joshua W.
AU - Samai, Poulami
AU - Jiang, Wenyan
AU - Marraffini, Luciano A.
N1 - Funding Information:
We are grateful to Philip M. Nussenzweig, Robert Heler, and Pascal Maguin for additional advice on deep sequencing of low-complexity amplicon pools. We are also grateful to Robert Heler for instructions on extracting selection coefficient values from fitness data. We would like to thank Seth Darst for advice on promoter inactivation, as well as Charlie Mo for advice on active site mutations in proteins of the LexA superfamily. Finally, we would like to thank The Rockefeller University Genomics Resource Center for deep sequencing library preparation. L.A.M. is supported by the Burroughs Wellcome Fund PATH Award, an NIH Director’s Pioneer Award (DP1GM128184-01) and a HHMI-Simons Faculty Scholar Award.
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-02557-2
DO - 10.1038/s41467-017-02557-2
M3 - Article
C2 - 29302058
AN - SCOPUS:85040248593
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 61
ER -