ArticlePLoS genetics2014
Telomeric ORFs (TLOs) in Candida spp. Encode mediator subunits that regulate distinct virulence traits.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 37 citations in OpenAlex.
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- Deletion of the Candida albicans TLO gene family using CRISPR-Cas9 mutagenesis allows characterisation of functional differences in α-, β- and γ- TLO gene function.PLoS genetics · 2023Article
- The role of the Mediator complex in fungal pathogenesis and response to antifungal agents.Essays in biochemistry · 2023Review
- Mediator Subunit Med15 Regulates Cell Morphology and Mating inJournal of fungi (Basel, Switzerland) · 2023Article
- Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process.PLoS genetics · 2022Article
- Architectural groups of a subtelomeric gene family evolve along distinct paths in Candida albicans.G3 (Bethesda, Md.) · 2022Article
- Stress- and metabolic responses of Candida albicans require Tor1 kinase N-terminal HEAT repeats.PLoS pathogens · 2022Article
- Telomeric and Sub-Telomeric Structure and Implications in Fungal Opportunistic Pathogens.Microorganisms · 2021Review
- Candida glabrata Yap6 Recruits Med2 To Alter Glycerophospholipid Composition and Develop Acid pH Stress Resistance.Applied and environmental microbiology · 2020Article
- Regulatory mechanisms controlling morphology and pathogenesis in Candida albicans.Current opinion in microbiology · 2019Review
- Spectrum of Trained Innate Immunity Induced by Low-VirulenceInfection and immunity · 2019Article
- Role of Mediator in virulence and antifungal drug resistance in pathogenic fungi.Current genetics · 2019Review
- Article
- Functional diversification accompanies gene family expansion of MED2 homologs in Candida albicans.PLoS genetics · 2018Article
- Article
- Mediator Tail Module Is Required for Tac1-ActivatedAntimicrobial agents and chemotherapy · 2017Article
- A Matter of Scale and Dimensions: Chromatin of Chromosome Landmarks in the Fungi.Microbiology spectrum · 2017Review
- Sir2 regulates stability of repetitive domains differentially in the human fungal pathogen Candida albicans.Nucleic acids research · 2016Article
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12 authors at 5 institutions in 3 countries.
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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 tlo1Δ/tlo2Δ 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 tlo1Δ/tlo2Δ 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 tlo1Δ/tlo2Δ null mutant indicates roles for Tlo proteins in transcriptional activation and repression. Complementation of the tlo1Δ/tlo2Δ 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.
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