Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting

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• dc.contributor.author Knödlseder, Nastassia
• dc.contributor.author Nevot, Guillermo
• dc.contributor.author Fábrega, María José
• dc.contributor.author Mir-Pedrol, Júlia
• dc.contributor.author Sanvicente-García, Marta
• dc.contributor.author Campamà-Sanz, Nil
• dc.contributor.author Paetzold, Bernhard, 1981-
• dc.contributor.author Lood, Rolf
• dc.contributor.author Güell Cargol, Marc, 1982-
• dc.date.accessioned 2022-06-15T06:29:02Z
• dc.date.available 2022-06-15T06:29:02Z
• dc.date.issued 2022
• dc.description.abstract Cutibacterium acnes (C. acnes) 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 acne vulgaris. The availability of the complete genome sequences from various C. acnes 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 C. acnes strains. To investigate the activity of these putative R-M and their relevance in host protective mechanisms, we analyzed the methylome of six representative C. acnes 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 C. acnes bacteriophage (PAD20) in killing various C. acnes 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Knödlseder N, Nevot G, Fábrega MJ, Mir-Pedrol J, Sanvicente-García M, Campamà-Sanz N, Paetzold B, Lood R, Güell M. Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting. PLoS Pathog. 2022 Mar 28;18(3):e1010420. DOI: 10.1371/journal.ppat.1010420
• dc.identifier.doi http://dx.doi.org/10.1371/journal.ppat.1010420
• dc.identifier.issn 1553-7366
• dc.identifier.uri http://hdl.handle.net/10230/53493
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS Pathog. 2022 Mar 28;18(3):e1010420
• dc.rights © 2022 Knödlseder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Bacteriophages
• dc.subject.keyword DNA methylation
• dc.subject.keyword Methylation
• dc.subject.keyword Genomics
• dc.subject.keyword Sequence motif analysis
• dc.subject.keyword RNA sequencing
• dc.subject.keyword Microbiome
• dc.subject.keyword CRISPR
• dc.title Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion