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dc.contributor.authorForde, BM
dc.contributor.authorPhan, M-D
dc.contributor.authorGawthorne, JA
dc.contributor.authorAshcroft, MM
dc.contributor.authorStanton-Cook, M
dc.contributor.authorSarkar, S
dc.contributor.authorPeters, KM
dc.contributor.authorChan, Kok Gan
dc.contributor.authorChong, TM
dc.contributor.authorYin, W-F
dc.contributor.authorUpton, Mathew
dc.contributor.authorSchembri, Mark
dc.contributor.authorBeatson, SA
dc.date.accessioned2016-04-18T15:24:54Z
dc.date.available2016-04-18T15:24:54Z
dc.date.issued2015-12-31
dc.identifier.issn2161-2129
dc.identifier.issn2150-7511
dc.identifier.otherARTN e01602-15
dc.identifier.urihttp://hdl.handle.net/10026.1/4511
dc.description.abstract

<jats:title>ABSTRACT</jats:title> <jats:p> <jats:named-content content-type="genus-species">Escherichia coli</jats:named-content> sequence type 131 (ST131) is a clone of uropathogenic <jats:named-content content-type="genus-species">E. coli</jats:named-content> that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of <jats:named-content content-type="genus-species">E. coli</jats:named-content> EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three <jats:sup>m6</jats:sup> A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for <jats:sup>m6</jats:sup> A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located. </jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant <jats:named-content content-type="genus-species">E. coli</jats:named-content> sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined <jats:named-content content-type="genus-species">E. coli</jats:named-content> clone. </jats:p>

dc.format.extente01602-e01615
dc.format.mediumElectronic
dc.languageen
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.subjectDNA Methylation
dc.subjectDNA, Bacterial
dc.subjectEscherichia coli Infections
dc.subjectGenotype
dc.subjectGlobal Health
dc.subjectHumans
dc.subjectMethyltransferases
dc.subjectUrinary Tract Infections
dc.subjectUropathogenic Escherichia coli
dc.titleLineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000367524700029&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue6
plymouth.volume6
plymouth.publication-statusPublished
plymouth.journalmBio
dc.identifier.doi10.1128/mbio.01602-15
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR)
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeUnited States
dc.identifier.eissn2150-7511
dc.rights.embargoperiodNo embargo
rioxxterms.versionofrecord10.1128/mbio.01602-15
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review


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