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dc.contributor.authorBlakeway, Luke V
dc.contributor.authorPower, Peter M
dc.contributor.authorJen, Freda E-C
dc.contributor.authorWorboys, Sam R
dc.contributor.authorBoitano, Matthew
dc.contributor.authorClark, Tyson A
dc.contributor.authorKorlach, Jonas
dc.contributor.authorBakaletz, Lauren O
dc.contributor.authorJennings, Michael P
dc.contributor.authorPeak, Ian R
dc.contributor.authorSeib, Kate L
dc.date.accessioned2017-09-19T12:30:29Z
dc.date.available2017-09-19T12:30:29Z
dc.date.issued2014
dc.identifier.issn0892-6638
dc.identifier.doi10.1096/fj.14-256578
dc.identifier.urihttp://hdl.handle.net/10072/67293
dc.description.abstractMoraxella catarrhalis is a significant cause of otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we characterize a phase-variable DNA methyltransferase (ModM), which contains 5'-CAAC-3' repeats in its open reading frame that mediate high-frequency mutation resulting in reversible on/off switching of ModM expression. Three modM alleles have been identified (modM1-3), with modM2 being the most commonly found allele. Using single-molecule, real-time (SMRT) genome sequencing and methylome analysis, we have determined that the ModM2 methylation target is 5'-GARm6AC-3', and 100% of these sites are methylated in the genome of the M. catarrhalis 25239 ModM2 on strain. Proteomic analysis of ModM2 on and off variants revealed that ModM2 regulates expression of multiple genes that have potential roles in colonization, infection, and protection against host defenses. Investigation of the distribution of modM alleles in a panel of M. catarrhalis strains, isolated from the nasopharynx of healthy children or middle ear effusions from patients with otitis media, revealed a statistically significant association of modM3 with otitis media isolates. The modulation of gene expression via the ModM phase-variable regulon (phasevarion), and the significant association of the modM3 allele with otitis media, suggests a key role for ModM phasevarions in the pathogenesis of this organism
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent4198731 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherFederation of American Societies for Experimental Biology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationY
dc.relation.ispartofpagefrom5197
dc.relation.ispartofpageto5207
dc.relation.ispartofissue12
dc.relation.ispartofjournalThe FASEB Journal
dc.relation.ispartofvolume28
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical bacteriology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode320701
dc.subject.fieldofresearchcode3208
dc.titleModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2014 Federation of American Societies for Experimental Biology. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
gro.date.issued2015-07-30T01:44:55Z
gro.hasfulltextFull Text
gro.griffith.authorJennings, Michael P.
gro.griffith.authorPeak, Ian
gro.griffith.authorJen, Freda E.
gro.griffith.authorSeib, Kate


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