DNA glycosylases provide antiviral defence in prokaryotes
Bacteria have adapted to phage predation by evolving a vast assortment of defence systems 1 . Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data 2 . Here, to overcome this limitation,...
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| Veröffentlicht in: | Nature (London) 2024-05, Vol.629 (8011), p.410-416 |
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| creator | Hossain, Amer A. Pigli, Ying Z. Baca, Christian F. Heissel, Søren Thomas, Alexis Libis, Vincent K. Burian, Ján Chappie, Joshua S. Brady, Sean F. Rice, Phoebe A. Marraffini, Luciano A. |
| description | Bacteria have adapted to phage predation by evolving a vast assortment of defence systems
1
. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data
2
. Here, to overcome this limitation, we infected
Escherichia coli
carrying a soil metagenomic DNA library
3
with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria–phage arms race.
A screen utilizing an environmental DNA library in
Escherichia coli
is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria. |
| doi_str_mv | 10.1038/s41586-024-07329-9 |
| format | Article |
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1
. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data
2
. Here, to overcome this limitation, we infected
Escherichia coli
carrying a soil metagenomic DNA library
3
with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria–phage arms race.
A screen utilizing an environmental DNA library in
Escherichia coli
is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-024-07329-9</identifier><identifier>PMID: 38632404</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/22 ; 45/23 ; 45/29 ; 631/326/1321 ; 631/326/41/2529 ; 82/58 ; Bacteria ; Bases (nucleic acids) ; Cloning ; Defense ; Deoxyribonucleic acid ; DNA ; DNA glycosylase ; E coli ; Genes ; Genomes ; Humanities and Social Sciences ; Immunity ; Infections ; Metagenomics ; multidisciplinary ; Phages ; Predation ; Prokaryotes ; Science ; Science (multidisciplinary)</subject><ispartof>Nature (London), 2024-05, Vol.629 (8011), p.410-416</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Nature Publishing Group May 9, 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-1a45277e298151e8b375acfa2ca980b5694edbeb5a8cd718fd86d33a12f29c7e3</citedby><cites>FETCH-LOGICAL-c475t-1a45277e298151e8b375acfa2ca980b5694edbeb5a8cd718fd86d33a12f29c7e3</cites><orcidid>0009-0008-1938-5795 ; 0000-0001-5967-8586 ; 0000-0003-2692-5602 ; 0000-0002-9163-0969 ; 0000-0002-3467-341X ; 0000-0002-4761-4742</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41586-024-07329-9$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41586-024-07329-9$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38632404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hossain, Amer A.</creatorcontrib><creatorcontrib>Pigli, Ying Z.</creatorcontrib><creatorcontrib>Baca, Christian F.</creatorcontrib><creatorcontrib>Heissel, Søren</creatorcontrib><creatorcontrib>Thomas, Alexis</creatorcontrib><creatorcontrib>Libis, Vincent K.</creatorcontrib><creatorcontrib>Burian, Ján</creatorcontrib><creatorcontrib>Chappie, Joshua S.</creatorcontrib><creatorcontrib>Brady, Sean F.</creatorcontrib><creatorcontrib>Rice, Phoebe A.</creatorcontrib><creatorcontrib>Marraffini, Luciano A.</creatorcontrib><title>DNA glycosylases provide antiviral defence in prokaryotes</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Bacteria have adapted to phage predation by evolving a vast assortment of defence systems
1
. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data
2
. Here, to overcome this limitation, we infected
Escherichia coli
carrying a soil metagenomic DNA library
3
with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria–phage arms race.
A screen utilizing an environmental DNA library in
Escherichia coli
is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria.</description><subject>45/22</subject><subject>45/23</subject><subject>45/29</subject><subject>631/326/1321</subject><subject>631/326/41/2529</subject><subject>82/58</subject><subject>Bacteria</subject><subject>Bases (nucleic acids)</subject><subject>Cloning</subject><subject>Defense</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA glycosylase</subject><subject>E coli</subject><subject>Genes</subject><subject>Genomes</subject><subject>Humanities and Social Sciences</subject><subject>Immunity</subject><subject>Infections</subject><subject>Metagenomics</subject><subject>multidisciplinary</subject><subject>Phages</subject><subject>Predation</subject><subject>Prokaryotes</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kTlPxDAQhS0EguX4AxQoEg1NwMc4diqEuCUEDdSW40yWQDZe7OxK--8xLHdBNcX75s0bPUJ2GT1kVOijCEzqIqcccqoEL_NyhYwYqCKHQqtVMqKU65xqUWyQzRifKKWSKVgnG0IXggOFESnPbk-ycbdwPi46GzFm0-DnbY2Z7Yd23gbbZTU22DvM2v5NfLZh4QeM22StsV3EnY-5RR4uzu9Pr_Kbu8vr05Ob3IGSQ84sSK4U8lIzyVBXQknrGsudLTWtZFEC1hVW0mpXK6abWhe1EJbxhpdOodgix0vf6ayaYO2wH1IoMw3tJCUx3rbmt9K3j2bs54YxqrQCmRwOPhyCf5lhHMykjQ67zvboZ9EICowLUAISuv8HffKz0Kf_EiWBMwZAE8WXlAs-xoDNVxpGzVs1ZlmNSdWY92pMmZb2fv7xtfLZRQLEEohJ6scYvm__Y_sKUueaAA</recordid><startdate>20240509</startdate><enddate>20240509</enddate><creator>Hossain, Amer A.</creator><creator>Pigli, Ying Z.</creator><creator>Baca, Christian F.</creator><creator>Heissel, Søren</creator><creator>Thomas, Alexis</creator><creator>Libis, Vincent K.</creator><creator>Burian, Ján</creator><creator>Chappie, Joshua S.</creator><creator>Brady, Sean F.</creator><creator>Rice, Phoebe A.</creator><creator>Marraffini, Luciano A.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>KL.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0009-0008-1938-5795</orcidid><orcidid>https://orcid.org/0000-0001-5967-8586</orcidid><orcidid>https://orcid.org/0000-0003-2692-5602</orcidid><orcidid>https://orcid.org/0000-0002-9163-0969</orcidid><orcidid>https://orcid.org/0000-0002-3467-341X</orcidid><orcidid>https://orcid.org/0000-0002-4761-4742</orcidid></search><sort><creationdate>20240509</creationdate><title>DNA glycosylases provide antiviral defence in prokaryotes</title><author>Hossain, Amer A. ; 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1
. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data
2
. Here, to overcome this limitation, we infected
Escherichia coli
carrying a soil metagenomic DNA library
3
with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria–phage arms race.
A screen utilizing an environmental DNA library in
Escherichia coli
is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38632404</pmid><doi>10.1038/s41586-024-07329-9</doi><tpages>7</tpages><orcidid>https://orcid.org/0009-0008-1938-5795</orcidid><orcidid>https://orcid.org/0000-0001-5967-8586</orcidid><orcidid>https://orcid.org/0000-0003-2692-5602</orcidid><orcidid>https://orcid.org/0000-0002-9163-0969</orcidid><orcidid>https://orcid.org/0000-0002-3467-341X</orcidid><orcidid>https://orcid.org/0000-0002-4761-4742</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 45/22 45/23 45/29 631/326/1321 631/326/41/2529 82/58 Bacteria Bases (nucleic acids) Cloning Defense Deoxyribonucleic acid DNA DNA glycosylase E coli Genes Genomes Humanities and Social Sciences Immunity Infections Metagenomics multidisciplinary Phages Predation Prokaryotes Science Science (multidisciplinary) |
| title | DNA glycosylases provide antiviral defence in prokaryotes |
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