Telomeric ORFs (TLOs) in Candida spp. Encode Mediator Subunits That Regulate Distinct Virulence Traits

• DOI: 10.1371/journal.pgen.1004658
• Publication Date: 2014-10-30T18:01:02Z
• Authors: John Haran; Hannah Boyle; Karsten Hokamp; Tim Yeomans; Zhongle Liu; Michael Church; Alastair B. Fleming; Matthew Z. Anderson; Judith Berman; Lawrence C. Myers; Derek J. Sullivan; Gary P. Moran
• Keywords: ORFS; Protein-fragment complementation assay; Candida dubliniensis; Wild type

The TLO genes are a family of telomere-associated ORFs in the fungal pathogens Candida albicans and C. dubliniensis that encode subunit Mediator complex with homology to Med2. more virulent pathogen has 15 copies gene whereas less pathogenic species only two (CdTLO1 CdTLO2). In this study we used as model investigate role regulating virulence also determine whether paralogs have evolved regulate distinct functions. A tlo1Δ/tlo2Δ mutant is unable form true hyphae, longer doubling times galactose broth, susceptible oxidative stress forms increased levels biofilm. Transcript profiling revealed expression starvation responses rich medium retarded hypha-induced transcripts serum. ChIP studies indicated Tlo1 binds many including exhibit high low under conditions analyzed. altered these null indicates roles for Tlo proteins transcriptional activation repression. Complementation TLO1, but not TLO2, restored wild-type filamentous growth, TLO2 fully suppressed biofilm growth. TLO1 had greater effect on broth. different abilities restore functions was supported by transcript showed hypha-specific (UME6, SOD5) utilisation (GAL1 GAL10), repression starvation-induced transcription. Thus, Tlo/Med2 encoding subunits properties spp. their expansion may account adaptability relative other species.