Open AccessEngineering selectivity of Cutibacterium acnes phages by epigenetic imprinting
Author(s) -
Nastassia Knödlseder,
Guillermo Nevot,
Maria-José Fábrega,
Júlia Mir-Pedrol,
Marta Sanvicente-García,
Nil Campamà Sanz,
Bernhard Paetzold,
Rolf Lood,
Marc Güell
Publication year - 2022
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010420
Subject(s) - biology , dna methylation , epigenetics , microbiology and biotechnology , methylation , bacteriophage , microbiome , propionibacterium acnes , gene , bacteria , genetics , gene expression , escherichia coli
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.