Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis.
Animals
Bacterial Proteins
/ genetics
Clostridioides difficile
/ enzymology
Clostridium Infections
/ microbiology
Cricetinae
DNA Methylation
DNA Modification Methylases
/ genetics
DNA, Bacterial
/ genetics
Epigenesis, Genetic
Epigenome
Gene Expression Regulation, Bacterial
Genetic Variation
Genome, Bacterial
/ genetics
Humans
Mice
Mutation
Nucleotide Motifs
Phylogeny
Regulatory Elements, Transcriptional
/ genetics
Spores, Bacterial
/ genetics
Substrate Specificity
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
14
08
2018
accepted:
18
10
2019
pubmed:
27
11
2019
medline:
18
7
2020
entrez:
27
11
2019
Statut:
ppublish
Résumé
Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections. Although considerable progress has been made in the understanding of its genome, the epigenome of C. difficile and its functional impact has not been systematically explored. Here, we perform a comprehensive DNA methylome analysis of C. difficile using 36 human isolates and observe a high level of epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity, the corresponding gene of which is highly conserved across our dataset and in all of the approximately 300 global C. difficile genomes examined. Inactivation of the methyltransferase gene negatively impacts sporulation, a key step in C. difficile disease transmission, and these results are consistently supported by multiomics data, genetic experiments and a mouse colonization model. Further experimental and transcriptomic analyses suggest that epigenetic regulation is associated with cell length, biofilm formation and host colonization. These findings provide a unique epigenetic dimension to characterize medically relevant biological processes in this important pathogen. This study also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomic studies.
Identifiants
pubmed: 31768029
doi: 10.1038/s41564-019-0613-4
pii: 10.1038/s41564-019-0613-4
pmc: PMC6925328
mid: NIHMS1541334
doi:
Substances chimiques
Bacterial Proteins
0
DNA, Bacterial
0
DNA Modification Methylases
EC 2.1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166-180Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007310
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI122232
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI107029
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114472
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120606
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131780
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI119145
Pays : United States
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