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dc.contributor.authorSrikhanta, Yogitha N
dc.contributor.authorDowideit, Stefanie J
dc.contributor.authorEdwards, Jennifer L
dc.contributor.authorFalsetta, Megan L
dc.contributor.authorWu, Hsing-Ju
dc.contributor.authorHarrison, Odile B
dc.contributor.authorFox, Kate L
dc.contributor.authorSeib, Kate L
dc.contributor.authorMaguire, Tina L
dc.contributor.authorWang, Andrew H-J
dc.contributor.authorMaiden, Martin C
dc.contributor.authorGrimmond, Sean M
dc.contributor.authorApicella, Michael A
dc.contributor.authorJennings, Michael P
dc.date.accessioned2017-05-03T13:23:30Z
dc.date.available2017-05-03T13:23:30Z
dc.date.issued2009
dc.date.modified2014-02-28T02:04:35Z
dc.identifier.issn1553-7366
dc.identifier.doi10.1371/journal.ppat.1000400
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent3346366 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoen_US
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome1000400-1
dc.relation.ispartofpagetoe1000400-22
dc.relation.ispartofissue4
dc.relation.ispartofjournalPLoS Pathogens
dc.relation.ispartofvolume5
dc.rights.retentionY
dc.subject.fieldofresearchMicrobial Genetics
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchcode060503
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1107
dc.subject.fieldofresearchcode1108
dc.titlePhasevarions mediate random switching of gene expression in pathogenic Neisseria
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://www.plos.org/journals/license.html
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)
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorSrikhanta, Yogitha N.
gro.griffith.authorSeib, Kate
gro.griffith.authorJennings, Michael P.


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