dc.contributor.author | HARAN, JOHN | en |
dc.contributor.author | FLEMING, ALASTAIR | en |
dc.contributor.author | HOKAMP, KARSTEN | en |
dc.date.accessioned | 2015-06-17T15:15:05Z | |
dc.date.available | 2015-06-17T15:15:05Z | |
dc.date.issued | 2014 | en |
dc.date.submitted | 2014 | en |
dc.identifier.citation | Haran 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, e1004658 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/74167 | |
dc.description | PUBLISHED | en |
dc.description.abstract | The
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
species | en |
dc.description.sponsorship | This 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.extent | e1004658 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | PLoS genetics | en |
dc.relation.ispartofseries | 10 | en |
dc.relation.ispartofseries | 10 | en |
dc.rights | Y | en |
dc.subject | Candida albicans | en |
dc.subject.lcsh | Candida albicans | en |
dc.title | Telomeric ORFs (TLOs) in Candida spp. Encode mediator subunits that regulate distinct virulence traits. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/kahokamp | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/fleminal | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/joharan | en |
dc.identifier.rssinternalid | 98991 | en |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.pgen.1004658 | en |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Genes & Society | en |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.subject.TCDTag | Genomes, Genomics | en |
dc.subject.TCDTag | Microbiology | en |
dc.subject.TCDTag | Molecular Biology | en |
dc.identifier.rssuri | http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004658 | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.contributor.sponsorGrantNumber | RFP.1/GEN/3044 | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.contributor.sponsorGrantNumber | RFP.1/GEN/3042 | en |
dc.contributor.sponsor | National Institutes of Health (NIH) | en |
dc.contributor.sponsorGrantNumber | R01AI075096 | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.contributor.sponsorGrantNumber | O4/IN3/B463 | en |