Derek Sullivan's Home Page

Molecular Oral Microbiology at the Dublin Dental University Hospital

The main theme of my research is the analysis of virulence in Candida species, in particular Candida dubliniensis and Candida albicans. This research involves the comparative analysis of the genomes and transcriptomes of these two very closely related species to identify the reasons for the disparity in their virulence. To date we have identified significant differences between the two species (e.g. absence of ALS3 and differential expression of SFL2 in C. dubliniensis) and we are currently investigating the role that these differences play in pathogenesis. Ongoing research into the epidemiology, population biology and drug resistance of Candida species is also a priority.



Representative recent publications:

1. Moran GP., Coleman DC. and Sullivan DJ. (2012) Candida albicans versus Candida dubliniensis: Why is C. albicans more pathogenic? International Journal of Microbiology  2012: pArticle ID 20592. PubMed

2. Agwu E, Ihongbe JC, McManus BA,Moran GP, Coleman DC, Sullivan DJ. (2012) Distribution of yeast species associated with oral lesions in HIV-infected patients in Southwest Uganda. Medical Mycology 50: 276 - 280. PubMed

3. Higgins J, Pinjon E, Oltean HN, White TC, Kelly SL, Martel CM, Sullivan DJ, Coleman DC, Moran GP. (2012) Triclosan antagonizes fluconazole activity against Candida albicans. Journal of Dental Research 91: 65 - 70. PubMed

4. Sullivan DJ, and Moran GP. (2011) Differential virulence of Candida albicans and C. dubliniensis: A role for Tor1 kinase? Virulence 2:77-81. PubMed

5. O'Connor, L., Caplice, N., Coleman, D.C., Sullivan, D.J. and Moran G.P. (2010) Differential filamentation of Candida albicans and C. dubliniensis is governed by nutrient regulation of UME6 expression. Eukaryotic Cell 9:1383-1397. PubMed

6. Spiering MJ, Moran GP, Chauvel M, MacCallum DM, Higgins J, Hokamp K, Yeomans T, d’Enfert C, Coleman DC, Sullivan DJ. (2010). Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model. Eukaryotic Cell 9:251-265. PubMed

7. Enjalbert B, Moran GP, Vaughan C, Yeomans T, MacCallum DM, Quinn J, Coleman DC, Brown AJ, Sullivan DJ. (2009). Genome-wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress. Molecular Microbiology 72:216-218. PubMed

8. Citiulo F, Moran GP, Coleman DC. Sullivan DJ. (2009). Purification and germination of Candida albicans and Candida dubliniensis chlamydospores cultured in liquid media. FEMS Yeast Research 9:1051-1060. PubMed

9. McManus BA, Sullivan DJ, Moran GP, d’Enfert C, Bougnoux ME, Nunn MA, Coleman DC. (2009). Genetic differences between avian and human isolates of Candida dubliniensis. Emerging Infectious Diseases 15:1467-1470. PubMed

10. McManus BA, Moran GP, Higgins JA, Sullivan DJ, Coleman DC. (2009). A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis. Antimicrobial Agents and Chemotherapy 53:4678-4685. PubMed

11. Jackson AP, Gamble JA, Yeomans T, Moran GP, Saunders D, Harris D, Aslett M, Barrell JF, Butler G, Citiulo F, Coleman DC, de Groot PW, Goodwin TJ, Quail MA, McQuillan J, Munro CA, Pain A, Poulter RT, Rajandream MA, Renauld H, Spiering MJ, Tivey A, Gow NA, Barrell B, Sullivan DJ, Berriman M. (2009). Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans. Genome Research 19:2231-2244. PubMed



Current Projects:

The role of the telomeric TLO genes in virulence of C. albicans and C. dubliniensis. 

Comparative genomic analysis has identified a dramatic difference in the size of the novel TLO gene family in C. albicans and C. dubliniensis. While there are 14 TLO genes in C. albicans there are only 2 present in C. dubliniensis. Preliminary data suggest that these genes encode a family of transcription factors involved in the control of morphogenesis and oxidative stress response. Together with Gary Moran at the DDUH, we are investigating the function of this novel telomeric gene family in growth and virulence in C. albicans

Funded by: Science Foundation Ireland
PhD students: John Haran and Hannah Boyle


The role of hyphae and hypha-specific genes in the pathogenesis of Candida dubliniensis.
The ability to produce hyphae is widely recognised as a major virulence determinant of C. albicans.  C. dubliniensis isolates fail to produce hyphae in a number of infection models and are missing a number of hypha-specific virulence genes.  We are currently investigating the effect of  increasing hypha formation and of expressing C. albicans-specific genes (e.g. ALS3 and HYR1) on the virulence  of C. dubliniensis.
Funded by: The Health Research Board
PhD student: Peter Hyde



Functional analysis of Filamentous Growth Regulator (FGR) genes and their role in the pathogenesis of Candida albicans


We propose that the absence of specific FGR genes in C. dubliniensis contributes to its reduced capacity to cause disease and that they contribute to the enhanced virulence of C. albicans. The function of the proteins encoded by these genes in C. albicans is currently unknown, however, we believe that investigation of their role will improve our understanding of how these fungi cause disease.

Funded by: Dublin Dental University Hospital and Trinity College Dublin studentship

PhD student: Isobel Scally


Contact Details

Address

Derek Sullivan
Division of Oral Biosciences
Dublin Dental University Hospital
Dublin 2
Ireland

Tel: +353-1-612-7275
Fax: +353 1 612 7295
email: Derek.Sullivan@dental.tcd.ie








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