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dc.contributor.authorSrikhanta, Yogitha N.en_AU
dc.contributor.authorDowideit, Stefanie J.en_AU
dc.contributor.authorEdwards, Jennifer L.en_AU
dc.contributor.authorFalsetta, Megan L.en_AU
dc.contributor.authorWu, Hsing-Juen_AU
dc.contributor.authorHarrison, Odile B.en_AU
dc.contributor.authorFox, Kate L.en_AU
dc.contributor.authorSeib, Kate L.en_AU
dc.contributor.authorMaguire, Tina L.en_AU
dc.contributor.authorWang, Andrew H.-J.en_AU
dc.contributor.authorMaiden, Martin C.en_AU
dc.contributor.authorGrimmond, Sean M.en_AU
dc.contributor.authorApicella, Michael A.en_AU
dc.contributor.authorJennings, Michael Paulen_AU
dc.date.accessioned2010-02-18en_AU
dc.date.accessioned2017-03-01T21:33:38Z
dc.date.available2017-03-01T21:33:38Z
dc.date.issued2009en_AU
dc.date.modified2010-09-10T05:18:16Z
dc.identifier.issn1553-7366en_AU
dc.identifier.doihttp://dx.doi.org/10.1371/journal.ppat.1000400en_AU
dc.identifier.urihttp://hdl.handle.net/10072/33886.1
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_AU
dc.description.peerreviewedYesen_AU
dc.description.publicationstatusYesen_AU
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Scienceen_AU
dc.publisher.placeUnited Statesen_AU
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrome1000400-1en_AU
dc.relation.ispartofpagetoe1000400-22en_AU
dc.relation.ispartofissue4en_AU
dc.relation.ispartofjournalPloS Pathogensen_AU
dc.relation.ispartofvolume5en_AU
dc.rights.retentionYen_AU
dc.subject.fieldofresearchEpigenetics (incl Genome Methylation and Epigenomics)en_AU
dc.subject.fieldofresearchGene Expression (incl Microarray and other genome-wide approaches)en_AU
dc.subject.fieldofresearchcode060404en_AU
dc.subject.fieldofresearchcode060405en_AU
dc.titlePhasevarions Mediate Random Switching of Gene Expression in Pathogenic Neisseriaen_AU
dc.typeJournal article
dc.type.descriptionJournal Articles (Refereed Article)en_AU
dc.type.codec1xen_AU
gro.facultyFaculty of Science, Environment, Engineering and Technologyen_AU
gro.date.issued2009
gro.hasfulltextNo Full Text


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