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Trinity College Dublin

Personal Information
Name Mc Manus, Brenda
Main Department Dental Science
College Title Research Fellow
E-mail bmcmanu@tcd.ie
College Tel  
 
Description of Research Interests
Collaborative investigation of Candida populations in Irish patients with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). My most recent research focused Irish patients with APECED, an autosomal recessive genetic disease that often manifests itself in the form of chronic mucocutaneous candidiasis. The study was carried out over 5 years in collaboration with dental clinicians in the DDUH, aiming to characterise the Candida population present in this group, and to correlate clinical signs of candidiasis with microbiological evidence of such. The genetic relatedness of Candida albicans isolates recovered during sequential clinical assessments of these patients was investigated, as was the effect of prophylactic intermittent antifungal therapy on the susceptibility of these isolates to azole antifungals. This study highlighted the need for microbiological diagnosis of candidiasis prior to the commencement of antifungal therapy in order to prevent unnecessary azole therapy and the development of azole resistance. Previous research focused on the use of multilocus sequence typing (MLST) to characterise the population structure of the pathogenic yeast Candida dubliniensis, and to compare the evolutionary biology of C. dubliniensis with that of its closest relative, C. albicans. The application of similar techniques to C. dubliniensis isolates recovered from seagulls showed that such isolates were genetically distinct to those recovered from human sources. One of the three specific clades in the population structure of C. dubliniensis is characterised by high-level resistance to the antifungal drug 5-fluorocytosine. My research demonstrated that the primary cause of this clade-specific resistance is a recessive Ser29Leu substitution in the cytosine deaminase. Further research into the evolutionary biology of C. dubliniensis will involve the comparative analysis of single nucleotide polymorphisms (SNPs) throughout the complete genomes of ten C. dubliniensis isolates representative of each MLST clade. Comparison of such SNPs with those in C. albicans may identify reasons why, despite their close genetic relationship, C. dubliniensis is significantly less pathogenic than C. albicans.
 
Research Interests
DNA Drug Resistance Epidemiology Eukaryotic gene regulation
Evolutionary genetics Gene Cloning Gene Expression Genetic Manipulation
Genetic/Molecular epidemiology Genomics Molecular Cloning Molecular genetics of gram positive pathogens
Molecular population genetics Nucleic Acids Oral diseases and Oral medicine Oral microbiology
Population structure and dynamics Prokaryotic and eukaryotic genetics and genomics Quantitative and molecular genetics
 
Publications and Other Research Outputs
Peer Reviewed
Molecular Epidemiology of Candida species. in, editor(s)Ashbee, HR. & Bignell, EM. , Handbook of Pathogenic Yeasts., Berlin Heidelberg, Springer Verlag, 2010, pp19 - 39, [Moran, G.P., McManus, B.A., Coleman, D.C. & D.J. Sullivan]
Notes: [Chapter 2 e-ISBN 978-3-642-03150-2]
COLEMAN DC, MORAN GP, McMANUS BA, SULLIVAN DJ, MECHANISMS OF ANTIFUNGAL DRUG RESISTANCE IN CANDIDA DUBLINIENSIS, FUTURE MICROBIOLOGY, 5, (6), 2010, p935-949
DOI  URL
McMANUS BA, SULLIVAN DJ, MORAN GP, D'ENFERT C, BOUGNOUX M-E, NUNN MA, AND COLEMAN DC, AVIAN-ASSOCIATED AND HUMAN ISOLATES OF Candida dubliniensis ARE GENETICALLY DISTINCT, EMERGING INFECTIOUS DISEASES, 15, (9), 2009, p1467-70
TARA - Full Text  DOI  URL
McManus BA, Coleman DC, Moran G, Pinjon E, Diogo D, Bougnoux ME, Borecká-Melkusova S, Bujdákova H, Murphy P, d'Enfert C, Sullivan DJ., Multilocus sequence typing reveals that the population structure of Candida dubliniensis is significantly less divergent than that of Candida albicans., Journal of Clinical Microbiology, 46, (2), 2008, p652 - 664
Notes: [ ]
TARA - Full Text
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