2026-04-13T02:23:36Zhttps://recercat.cat/oai/request
oai:recercat.cat:10230/534932025-12-26T11:25:32Zcom_2072_6col_2072_452952
RECERCAT author Knödlseder, Nastassia author Nevot, Guillermo author Fábrega, María José author Mir-Pedrol, Júlia author Sanvicente-García, Marta author Campamà-Sanz, Nil author Paetzold, Bernhard, 1981- author Lood, Rolf author Güell Cargol, Marc, 1982- 2022-06-15T06:29:02Z2022-06-15T06:29:02Z2022 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. © 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. http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Bacteriophages DNA methylation Methylation Genomics Sequence motif analysis RNA sequencing Microbiome CRISPR Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion