{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:46:44Z","timestamp":1791895604035,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010420","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000006","name":"Office of Naval Research","doi-asserted-by":"crossref","award":["N62909-18-1-2155"],"award-info":[{"award-number":["N62909-18-1-2155"]}],"id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018967","name":"Universitat Pompeu Fabra","doi-asserted-by":"publisher","award":["INNOV21-09-1 - SynFlora"],"award-info":[{"award-number":["INNOV21-09-1 - SynFlora"]}],"id":[{"id":"10.13039\/100018967","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Industria del Coneixement of the Catalan Government","award":["INNOV21-09-1 - SynFlora via AGAUR - IdC 2019 PROD 00057"],"award-info":[{"award-number":["INNOV21-09-1 - SynFlora via AGAUR - IdC 2019 PROD 00057"]}]},{"name":"Maria Maetzu-UPF","award":["AEI- MM-CEX2018-000792"],"award-info":[{"award-number":["AEI- MM-CEX2018-000792"]}]},{"name":"SEQC"},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["2021FI_B1 00128"],"award-info":[{"award-number":["2021FI_B1 00128"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Government","award":["Juan de la Cierva Fellowship, Award FJC 2018-037096-I"],"award-info":[{"award-number":["Juan de la Cierva Fellowship, Award FJC 2018-037096-I"]}]},{"name":"ONRx for the project Engineered Biofilms","award":["Award N62909-20-1-2086"],"award-info":[{"award-number":["Award N62909-20-1-2086"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Cutibacterium acnes (C<\/jats:italic>\n                    .\n                    <jats:italic>acnes)<\/jats:italic>\n                    is a gram-positive bacterium and a member of the human skin microbiome. Despite being the most abundant skin commensal, certain members have been associated with common inflammatory disorders such as\n                    <jats:italic>acne vulgaris<\/jats:italic>\n                    . The availability of the complete genome sequences from various\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>acnes<\/jats:italic>\n                    clades have enabled the identification of putative methyltransferases, some of them potentially belonging to restriction-modification (R-M) systems which protect the host of invading DNA. However, little is known on whether these systems are functional in the different\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>acnes<\/jats:italic>\n                    strains. To investigate the activity of these putative R-M and their relevance in host protective mechanisms, we analyzed the methylome of six representative\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>acnes<\/jats:italic>\n                    strains by Oxford Nanopore Technologies (ONT) sequencing. We detected the presence of a 6-methyladenine modification at a defined DNA consensus sequence in strain KPA171202 and recombinant expression of this R-M system confirmed its methylation activity. Additionally, a R-M knockout mutant verified the loss of methylation properties of the strain. We studied the potential of one\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>acnes<\/jats:italic>\n                    bacteriophage (PAD20) in killing various\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>acnes<\/jats:italic>\n                    strains and linked an increase in its specificity to phage DNA methylation acquired upon infection of a methylation competent strain. We demonstrate a therapeutic application of this mechanism where phages propagated in R-M deficient strains selectively kill R-M deficient acne-prone clades while probiotic ones remain resistant to phage infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010420","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T13:30:45Z","timestamp":1648474245000},"page":"e1010420","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting"],"prefix":"10.1371","volume":"18","author":[{"given":"Nastassia","family":"Kn\u00f6dlseder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Nevot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Jos\u00e9","family":"F\u00e1brega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Mir-Pedrol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sanvicente-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil","family":"Campam\u00e0-Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Paetzold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Lood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-7912","authenticated-orcid":true,"given":"Marc","family":"G\u00fcell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ppat.1010420.ref001","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cub.2015.12.041","article-title":"Bacterial Autoimmunity Due to a Restriction-Modification System","volume":"26","author":"M Ple\u0161ka","year":"2016","journal-title":"Curr Biol"},{"key":"ppat.1010420.ref002","doi-asserted-by":"crossref","first-page":"11454","DOI":"10.1073\/pnas.1820256116","article-title":"Systematic evasion of the restriction-modification barrier in bacteria","volume":"116","author":"CD Johnston","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010420.ref003","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gku734","article-title":"The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts","volume":"42","author":"PH Oliveira","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010420.ref004","doi-asserted-by":"crossref","first-page":"e1005854","DOI":"10.1371\/journal.pgen.1005854","article-title":"The Epigenomic Landscape of Prokaryotes","volume":"12","author":"MJ Blow","year":"2016","journal-title":"PLoS Genet"},{"key":"ppat.1010420.ref005","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1128\/MMBR.00044-12","article-title":"Diverse functions of restriction-modification systems in addition to cellular defense","volume":"77","author":"K Vasu","year":"2013","journal-title":"Microbiol Mol Biol Rev"},{"key":"ppat.1010420.ref006","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1093\/nar\/gkg274","article-title":"A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes","author":"RJ Roberts","year":"2003","journal-title":"Nucleic Acids Research"},{"key":"ppat.1010420.ref007","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1128\/jb.88.6.1652-1660.1964","article-title":"GENETIC CONTROL OF RESTRICTION AND MODIFICATION IN ESCHERICHIA COLI1","author":"H. Boyer","year":"1964","journal-title":"Journal of Bacteriology"},{"key":"ppat.1010420.ref008","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrmicro.2017.157","article-title":"The human skin microbiome","volume":"16","author":"AL Byrd","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1010420.ref009","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1365-2133.2008.08437.x","article-title":"Skin microbiota: a source of disease or defence?","author":"AL Cogen","year":"2008","journal-title":"British Journal of Dermatology"},{"key":"ppat.1010420.ref010","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1586\/eri.11.137","article-title":"Propionibacterium acnes: infection beyond the skin","volume":"9","author":"A Perry","year":"2011","journal-title":"Expert Rev Anti Infect Ther"},{"key":"ppat.1010420.ref011","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1128\/CMR.00092-13","article-title":"Propionibacterium acnes: from 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