Cargando…

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

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 lysogeni...

Descripción completa

Detalles Bibliográficos
Autores principales: Goldberg, Gregory W., McMillan, Elizabeth A., Varble, Andrew, Modell, Joshua W., Samai, Poulami, Jiang, Wenyan, Marraffini, Luciano A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754349/
https://www.ncbi.nlm.nih.gov/pubmed/29302058
http://dx.doi.org/10.1038/s41467-017-02557-2
_version_ 1783290395685289984
author Goldberg, Gregory W.
McMillan, Elizabeth A.
Varble, Andrew
Modell, Joshua W.
Samai, Poulami
Jiang, Wenyan
Marraffini, Luciano A.
author_facet Goldberg, Gregory W.
McMillan, Elizabeth A.
Varble, Andrew
Modell, Joshua W.
Samai, Poulami
Jiang, Wenyan
Marraffini, Luciano A.
author_sort Goldberg, Gregory W.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5754349
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57543492018-01-12 Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts Goldberg, Gregory W. McMillan, Elizabeth A. Varble, Andrew Modell, Joshua W. Samai, Poulami Jiang, Wenyan Marraffini, Luciano A. Nat Commun Article 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. Nature Publishing Group UK 2018-01-04 /pmc/articles/PMC5754349/ /pubmed/29302058 http://dx.doi.org/10.1038/s41467-017-02557-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Goldberg, Gregory W.
McMillan, Elizabeth A.
Varble, Andrew
Modell, Joshua W.
Samai, Poulami
Jiang, Wenyan
Marraffini, Luciano A.
Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
title Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
title_full Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
title_fullStr Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
title_full_unstemmed Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
title_short Incomplete prophage tolerance by type III-A CRISPR-Cas systems reduces the fitness of lysogenic hosts
title_sort incomplete prophage tolerance by type iii-a crispr-cas systems reduces the fitness of lysogenic hosts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754349/
https://www.ncbi.nlm.nih.gov/pubmed/29302058
http://dx.doi.org/10.1038/s41467-017-02557-2
work_keys_str_mv AT goldberggregoryw incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts
AT mcmillanelizabetha incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts
AT varbleandrew incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts
AT modelljoshuaw incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts
AT samaipoulami incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts
AT jiangwenyan incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts
AT marraffinilucianoa incompleteprophagetolerancebytypeiiiacrisprcassystemsreducesthefitnessoflysogenichosts