Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence
BREX (for BacteRiophage EXclusion) is a superfamily of common bacterial and archaeal defence systems active against diverse bacteriophages. While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by...
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Veröffentlicht in: | Nucleic acids research 2020-06, Vol.48 (10), p.5397-5406 |
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creator | Isaev, Artem Drobiazko, Alena Sierro, Nicolas Gordeeva, Julia Yosef, Ido Qimron, Udi Ivanov, Nikolai V Severinov, Konstantin |
description | BREX (for BacteRiophage EXclusion) is a superfamily of common bacterial and archaeal defence systems active against diverse bacteriophages. While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction-modification systems, is also active against BREX. In contrast to the wild-type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. The result suggests that, similar to its action against type I R-M systems, Ocr associates with as yet unidentified BREX system complexes containing BrxX and neutralizes their ability to both methylate and exclude incoming phage DNA. |
doi_str_mv | 10.1093/nar/gkaa290 |
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While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction-modification systems, is also active against BREX. In contrast to the wild-type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. The result suggests that, similar to its action against type I R-M systems, Ocr associates with as yet unidentified BREX system complexes containing BrxX and neutralizes their ability to both methylate and exclude incoming phage DNA.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkaa290</identifier><identifier>PMID: 32338761</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Bacteriophage T7 - genetics ; Bacteriophage T7 - physiology ; DNA Methylation ; DNA Modification Methylases - metabolism ; Escherichia coli - enzymology ; Escherichia coli - genetics ; Escherichia coli - virology ; Gene regulation, Chromatin and Epigenetics ; Plasmids ; Viral Proteins - genetics ; Viral Proteins - metabolism</subject><ispartof>Nucleic acids research, 2020-06, Vol.48 (10), p.5397-5406</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><rights>The Author(s) 2020. 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While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction-modification systems, is also active against BREX. In contrast to the wild-type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. The result suggests that, similar to its action against type I R-M systems, Ocr associates with as yet unidentified BREX system complexes containing BrxX and neutralizes their ability to both methylate and exclude incoming phage DNA.</description><subject>Bacteriophage T7 - genetics</subject><subject>Bacteriophage T7 - physiology</subject><subject>DNA Methylation</subject><subject>DNA Modification Methylases - metabolism</subject><subject>Escherichia coli - enzymology</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - virology</subject><subject>Gene regulation, Chromatin and Epigenetics</subject><subject>Plasmids</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - metabolism</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1LAzEQhoMotlZP3iVHQVYzyWZ3cxFqWz-gWJEK3kI2m7TR_ajJVvDfu9Ja9DQM8_DOy4PQKZBLIIJd1cpfLd6VooLsoT6whEaxSOg-6hNGeAQkznroKIQ3QiAGHh-iHqOMZWkCfTR-WqqFwfMUjx-HuHKV03jlm9a4Gs-0xy5ghVfdXrfY1UuXu7bxuLH45nnyigtjTa3NMTqwqgzmZDsH6OV2Mh_dR9PZ3cNoOI00y6CNgIlCU26LmCoKjObaWJXbNEtZ1zFVHIjNDACQlAiRcarTmOfGkoTEXHHBBuh6k7ta55UpdFfKq1KuvKuU_5KNcvL_pXZLuWg-ZUoTgIx1AefbAN98rE1oZeWCNmWpatOsg6RMcMo5SeIOvdig2jcheGN3b4DIH--y8y633jv67G-zHfsrmn0DgEF9sA</recordid><startdate>20200604</startdate><enddate>20200604</enddate><creator>Isaev, Artem</creator><creator>Drobiazko, Alena</creator><creator>Sierro, Nicolas</creator><creator>Gordeeva, Julia</creator><creator>Yosef, Ido</creator><creator>Qimron, Udi</creator><creator>Ivanov, Nikolai V</creator><creator>Severinov, Konstantin</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9904-1715</orcidid><orcidid>https://orcid.org/0000-0002-2052-4333</orcidid><orcidid>https://orcid.org/0000-0001-9706-450X</orcidid></search><sort><creationdate>20200604</creationdate><title>Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence</title><author>Isaev, Artem ; Drobiazko, Alena ; Sierro, Nicolas ; Gordeeva, Julia ; Yosef, Ido ; Qimron, Udi ; Ivanov, Nikolai V ; Severinov, Konstantin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-139dc25fd42a2132bcefabf78730487a510f8e11107099852c745bef06045a593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Bacteriophage T7 - genetics</topic><topic>Bacteriophage T7 - physiology</topic><topic>DNA Methylation</topic><topic>DNA Modification Methylases - metabolism</topic><topic>Escherichia coli - enzymology</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli - virology</topic><topic>Gene regulation, Chromatin and Epigenetics</topic><topic>Plasmids</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isaev, Artem</creatorcontrib><creatorcontrib>Drobiazko, Alena</creatorcontrib><creatorcontrib>Sierro, Nicolas</creatorcontrib><creatorcontrib>Gordeeva, Julia</creatorcontrib><creatorcontrib>Yosef, Ido</creatorcontrib><creatorcontrib>Qimron, Udi</creatorcontrib><creatorcontrib>Ivanov, Nikolai V</creatorcontrib><creatorcontrib>Severinov, Konstantin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isaev, Artem</au><au>Drobiazko, Alena</au><au>Sierro, Nicolas</au><au>Gordeeva, Julia</au><au>Yosef, Ido</au><au>Qimron, Udi</au><au>Ivanov, Nikolai V</au><au>Severinov, Konstantin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2020-06-04</date><risdate>2020</risdate><volume>48</volume><issue>10</issue><spage>5397</spage><epage>5406</epage><pages>5397-5406</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>BREX (for BacteRiophage EXclusion) is a superfamily of common bacterial and archaeal defence systems active against diverse bacteriophages. While the mechanism of BREX defence is currently unknown, self versus non-self differentiation requires methylation of specific asymmetric sites in host DNA by BrxX (PglX) methyltransferase. Here, we report that T7 bacteriophage Ocr, a DNA mimic protein that protects the phage from the defensive action of type I restriction-modification systems, is also active against BREX. In contrast to the wild-type phage, which is resistant to BREX defence, T7 lacking Ocr is strongly inhibited by BREX, and its ability to overcome the defence could be complemented by Ocr provided in trans. We further show that Ocr physically associates with BrxX methyltransferase. Although BREX+ cells overproducing Ocr have partially methylated BREX sites, their viability is unaffected. 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subjects | Bacteriophage T7 - genetics Bacteriophage T7 - physiology DNA Methylation DNA Modification Methylases - metabolism Escherichia coli - enzymology Escherichia coli - genetics Escherichia coli - virology Gene regulation, Chromatin and Epigenetics Plasmids Viral Proteins - genetics Viral Proteins - metabolism |
title | Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence |
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