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dc.contributor.authorHARAN, JOHNen
dc.contributor.authorFLEMING, ALASTAIRen
dc.contributor.authorHOKAMP, KARSTENen
dc.date.accessioned2015-06-17T15:15:05Z
dc.date.available2015-06-17T15:15:05Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationHaran J, Boyle H, Hokamp K, Yeomans T, Liu Z, Church M, Fleming AB, Anderson MZ, Berman J, Myers LC, Sullivan DJ, Moran GP, Telomeric ORFs (TLOs) in Candida spp. Encode mediator subunits that regulate distinct virulence traits., PLoS genetics, 10, 10, 2014, e1004658en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/74167
dc.descriptionPUBLISHEDen
dc.description.abstractThe TLO genes are a family of telomere-associated ORFs in the fungal pathogens Candida albicans and C. dubliniensis that encode a subunit of the Mediator complex with homology to Med2. The more virulent pathogen C. albicans has 15 copies of the gene whereas the less pathogenic species C. dubliniensis has only two ( CdTLO1 and CdTLO2 ). In this study we used C. dubliniensis as a model to investigate the role of TLO genes in regulating virulence and also to determine whether TLO paralogs have evolved to regulate distinct functions. A C. dubliniensis tlo1 D / tlo2 D mutant is unable to form true hyphae, has longer doubling times in galactose broth, is more susceptible to oxidative stress and forms increased levels of biofilm. Transcript profiling of the tlo1 D / tlo2 D mutant revealed increased expression of starvation responses in rich medium and retarded expression of hypha-induced transcripts in serum. ChIP studies indicated that Tlo1 binds to many ORFs including genes that exhibit high and low expression levels under the conditions analyzed. The altered expression of these genes in the tlo1 D / tlo2 D null mutant indicates roles for Tlo proteins in transcriptional activation and repression. Complementation of the tlo1 D / tlo2 D mutant with TLO1 , but not TLO2 , restored wild-type filamentous growth, whereas only TLO2 fully suppressed biofilm growth. Complementation with TLO1 also had a greater effect on doubling times in galactose broth. The different abilities of TLO1 and TLO2 to restore wild-type functions was supported by transcript profiling studies that showed that only TLO1 restored expression of hypha-specific genes ( UME6, SOD5 ) and galactose utilisation genes ( GAL1 and GAL10 ), whereas TLO2 restored repression of starvation-induced gene transcription. Thus, Tlo/Med2 paralogs encoding Mediator subunits regulate different virulence properties in Candida spp. and their expansion may account for the increased adaptability of C. albicans relative to other Candida speciesen
dc.description.sponsorshipThis project was funded by Science Foundation Ireland, grant numbers RFP.1/GEN/3044, RFP.1/GEN/3042 and O4/IN3/B463 to GPM and DJS (www.SFI. ie). JB was supported by the NIH, grant number R01AI075096. JH was supported by the Faculty of Health Sciences, Trinity College Dublin and by an award fr om the Society for General Microbiology President’s fund to visit the laboratory of JB. The funders had no role in study design, data collection and analy sis, decision to publish, or preparation of the manuscript.en
dc.format.extente1004658en
dc.language.isoenen
dc.relation.ispartofseriesPLoS geneticsen
dc.relation.ispartofseries10en
dc.relation.ispartofseries10en
dc.rightsYen
dc.subjectCandida albicansen
dc.subject.lcshCandida albicansen
dc.titleTelomeric ORFs (TLOs) in Candida spp. Encode mediator subunits that regulate distinct virulence traits.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.contributor.sponsorNational Institutes of Health (NIH)en
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kahokampen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/fleminalen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/joharanen
dc.identifier.rssinternalid98991en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1004658en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumberRFP.1/GEN/3044en
dc.contributor.sponsorGrantNumberRFP.1/GEN/3042en
dc.contributor.sponsorGrantNumberR01AI075096en
dc.contributor.sponsorGrantNumberO4/IN3/B463en
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.subject.TCDTagGenomes, Genomicsen
dc.subject.TCDTagMicrobiologyen
dc.subject.TCDTagMolecular Biologyen
dc.identifier.rssurihttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004658en


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