dc.contributor.author | Srikhanta, Yogitha N. | en_AU |
dc.contributor.author | Dowideit, Stefanie J. | en_AU |
dc.contributor.author | Edwards, Jennifer L. | en_AU |
dc.contributor.author | Falsetta, Megan L. | en_AU |
dc.contributor.author | Wu, Hsing-Ju | en_AU |
dc.contributor.author | Harrison, Odile B. | en_AU |
dc.contributor.author | Fox, Kate L. | en_AU |
dc.contributor.author | Seib, Kate L. | en_AU |
dc.contributor.author | Maguire, Tina L. | en_AU |
dc.contributor.author | Wang, Andrew H.-J. | en_AU |
dc.contributor.author | Maiden, Martin C. | en_AU |
dc.contributor.author | Grimmond, Sean M. | en_AU |
dc.contributor.author | Apicella, Michael A. | en_AU |
dc.contributor.author | Jennings, Michael Paul | en_AU |
dc.date.accessioned | 2010-02-18 | en_AU |
dc.date.accessioned | 2017-03-01T21:33:38Z | |
dc.date.available | 2017-03-01T21:33:38Z | |
dc.date.issued | 2009 | en_AU |
dc.date.modified | 2010-09-10T05:18:16Z | |
dc.identifier.issn | 1553-7366 | en_AU |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.ppat.1000400 | en_AU |
dc.identifier.uri | http://hdl.handle.net/10072/33886.1 | |
dc.description.abstract | Many 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.peerreviewed | Yes | en_AU |
dc.description.publicationstatus | Yes | en_AU |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Public Library of Science | en_AU |
dc.publisher.place | United States | en_AU |
dc.relation.ispartofstudentpublication | N | en_AU |
dc.relation.ispartofpagefrom | e1000400-1 | en_AU |
dc.relation.ispartofpageto | e1000400-22 | en_AU |
dc.relation.ispartofissue | 4 | en_AU |
dc.relation.ispartofjournal | PloS Pathogens | en_AU |
dc.relation.ispartofvolume | 5 | en_AU |
dc.rights.retention | Y | en_AU |
dc.subject.fieldofresearch | Epigenetics (incl Genome Methylation and Epigenomics) | en_AU |
dc.subject.fieldofresearch | Gene Expression (incl Microarray and other genome-wide approaches) | en_AU |
dc.subject.fieldofresearchcode | 060404 | en_AU |
dc.subject.fieldofresearchcode | 060405 | en_AU |
dc.title | Phasevarions Mediate Random Switching of Gene Expression in Pathogenic Neisseria | en_AU |
dc.type | Journal article | |
dc.type.description | Journal Articles (Refereed Article) | en_AU |
dc.type.code | c1x | en_AU |
gro.faculty | Faculty of Science, Environment, Engineering and Technology | en_AU |
gro.date.issued | 2009 | |
gro.hasfulltext | No Full Text | |