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dc.contributor.authorSrikhanta, Yogitha N.en_US
dc.contributor.authorDowideit, Stefanie J.en_US
dc.contributor.authorEdwards, Jennifer L.en_US
dc.contributor.authorFalsetta, Megan L.en_US
dc.contributor.authorWu, Hsing-Juen_US
dc.contributor.authorHarrison, Odile B.en_US
dc.contributor.authorFox, Kate L.en_US
dc.contributor.authorSeib, Kate L.en_US
dc.contributor.authorMaguire, Tina L.en_US
dc.contributor.authorWang, Andrew H.-J.en_US
dc.contributor.authorMaiden, Martin C. J.en_US
dc.contributor.authorGrimmond, Sean M.en_US
dc.contributor.authorApicella, Michael A.en_US
dc.contributor.authorJennings, Michael P.en_US
dc.date.accessioned2017-05-03T13:23:30Z
dc.date.available2017-05-03T13:23:30Z
dc.date.issued2010en_US
dc.date.modified2014-02-28T02:04:35Z
dc.identifier.issn1553-7366en_US
dc.identifier.doi10.1371/journal.ppat.1000400en_US
dc.identifier.urihttp://hdl.handle.net/10072/33623
dc.description.abstractMany host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae, the random switching of the modA gene controls expression of a phase-variable regulon of genes (a ''phasevarion''), via differential methylation of the genome in the modA ON and OFF states. Phase-variable mod genes are also present in Neisseria meningitidis and Neisseria gonorrhoeae, suggesting that phasevarions may occur in these important human pathogens. Phylogenetic studies on phase-variable mod genes associated with type III restriction modification (R-M) systems revealed that these organisms have two distinct mod genes-modA and modB. There are also distinct alleles of modA (abundant: modA11, 12, 13; minor: modA4, 15, 18) and modB (modB1, 2). These alleles differ only in their DNA recognition domain. ModA11 was only found in N. meningitidis and modA13 only in N. gonorrhoeae. The recognition site for the modA13 methyltransferase in N. gonorrhoeae strain FA1090 was identified as 5'-AGAAA-3'. Mutant strains lacking the modA11, 12 or 13 genes were made in N. meningitidis and N. gonorrhoeae and their phenotype analyzed in comparison to a corresponding mod ON wild-type strain. Microarray analysis revealed that in all three modA alleles multiple genes were either upregulated or downregulated, some of which were virulence-associated. For example, in N. meningitidis MC58 (modA11), differentially expressed genes included those encoding the candidate vaccine antigens lactoferrin binding proteins A and B. Functional studies using N. gonorrhoeae FA1090 and the clinical isolate O1G1370 confirmed that modA13 ON and OFF strains have distinct phenotypes in antimicrobial resistance, in a primary human cervical epithelial cell model of infection, and in biofilm formation. This study, in conjunction with our previous work in H. influenzae, indicates that phasevarions may be a common strategy used by host-adapted bacterial pathogens to randomly switch between ''differentiated'' cell types.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.format.extent3346366 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefrome1000400-1en_US
dc.relation.ispartofpagetoe1000400-22en_US
dc.relation.ispartofissue4en_US
dc.relation.ispartofjournalPLoS Pathogensen_US
dc.relation.ispartofvolume5en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchMicrobial Geneticsen_US
dc.subject.fieldofresearchcode060503en_US
dc.titlePhasevarions mediate random switching of gene expression in pathogenic Neisseriaen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
dcterms.licensehttp://www.plos.org/journals/license.htmlen_US
gro.rights.copyright© 2010 Srikhanta et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)en_US
gro.date.issued2010
gro.hasfulltextFull Text


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