Dental School Researchers Achieve Major Breakthrough in Fungal Pathogenesis
Posted on: 11 December 2014
Candida species are a group of yeasts that are increasingly associated with life threatening infections in immunocompromised patients, as well as common oral and vaginal thrush. Researchers in the School of Dental Science, Trinity College Dublin, have identified a group of novel regulatory genes that control virulence in these infectious organisms.
The team lead by Research Director at the School of Dental Science, Dr Gary Moran and Professor in Microbiology, Trinity, Derek Sullivan have characterised a family of genes, normally found at the ends of chromosomes (telomeres) that regulate key pathogenic traits. The genes, dubbed TLOs due to their telomeric location, encode subunits of a complex with a central role in gene transcription called Mediator. Most organisms possess only one gene encoding this subunit, however some Candida species have been shown to have multiple copies located at the telomeres. The most virulent species Candida albicans has 14 copies of the TLO gene whereas the less pathogenic species Candida dubliniensis has only two (TLO1 and TLO2).
The team showed for the first time that TLO genes were involved in the regulation of key pathogenic traits, raising the possibility that TLOs could be a target for novel therapies to control fungal diseases.
Transcriptional profiling and chromatin immunoprecipitation (ChIP) showed that TLOs were required for rapid induction of genes required for filamentous growth, stress resistance and nutrient acquisition, key processes in colonisation and infection of the host.
Two graduate students in the School of Dental Science, John Haran and Hannah Boyle carried out the majority of the work which has been recently published in PLoS Genetics. The work also involved collaborators in the School of Genetics and Microbiology (Assistant Professor in Microbiology, Alastair Fleming, Michael Church and Research Fellow in Genetics, Karsten Hokamp) as well as international collaborators in the University of Minnesota and Geisel Medical School at Dartmouth. The work was supported by Science Foundation Ireland (SFI), the Society for General Microbiology (SGM) and the Faculty of Health Sciences TCD.
The paper Telomeric ORFs (TLOs) in Candida spp. encode Mediator subunits that regulate distinct virulence traits. J. Haran, H. Boyle, K. Hokamp, T. Yeomans, Z. Liu, M. Church, A.B. Fleming, M. Z. Anderson, J. Berman, L.C. Myers, D.J. Sullivan & G.P. Moran. PLoS Genetics, is available here: http://www.plosgenetics.org/doi/pgen.1004658