Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting
(2022) In PLoS Pathogens 18(3).- 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 restrictionmodification (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... (More)
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 restrictionmodification (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.
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- author
- Knödlseder, Nastassia ; Nevot, Guillermo ; Fábrega, Maria Jose ; Mir-Pedrol, Julia ; Sanvicente-García, Marta ; Campamà-Sanz, Nil ; Paetzold, Bernhard ; Lood, Rolf LU and Güell, Marc
- organization
- publishing date
- 2022-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 18
- issue
- 3
- article number
- e1010420
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- scopus:85127339932
- pmid:35344565
- ISSN
- 1553-7366
- DOI
- 10.1371/journal.ppat.1010420
- language
- English
- LU publication?
- yes
- id
- f8be4797-f8d7-4d11-a160-6c02e53eb1e0
- date added to LUP
- 2022-06-03 11:47:05
- date last changed
- 2024-06-27 21:11:22
@article{f8be4797-f8d7-4d11-a160-6c02e53eb1e0,
abstract = {{<p>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 restrictionmodification (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.</p>}},
author = {{Knödlseder, Nastassia and Nevot, Guillermo and Fábrega, Maria Jose and Mir-Pedrol, Julia and Sanvicente-García, Marta and Campamà-Sanz, Nil and Paetzold, Bernhard and Lood, Rolf and Güell, Marc}},
issn = {{1553-7366}},
language = {{eng}},
number = {{3}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Pathogens}},
title = {{Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting}},
url = {{http://dx.doi.org/10.1371/journal.ppat.1010420}},
doi = {{10.1371/journal.ppat.1010420}},
volume = {{18}},
year = {{2022}},
}