Abstract
INTRODUCTION: Recent studies have demonstrated the potential of Aspergillus fumigatus to form biofilm structures similar to those identified with Candida albicans. In contrast to the wide berth of knowledge relating to the biology of C. albicans biofilms, relatively little is known regarding the development and morphology of multicellular communities of A. fumigatus. This alternate lifestyle may have profound clinical implications with regard to the pathogenic potential of the organism and the likelihood of successful detection and treatment.METHODS: A reproducible biofilm model of A. fumigatus was developed using several different substrates, which were used to macroscopically and microscopically investigate the phenotypic attributes and general characteristics of biofilm formation, and to investigate antifungal susceptibility profiles. Transcriptional analysis of three key distinct phases of biofilm formation was then performed with in vitro samples, with further analysis using in vivo aspergillosis samples from a guinea pig. Further analysis was performed with competitive bacterial species and its own secreted metabolites with an aim to identify possible novel anti- aspergillus agents.
RESULTS: A robust and reproducible biofilm model for A. fumigatus was developed. Biofilms of A. fumigatus displayed the typical characteristics associated with sessile growth, namely reduced antifungal susceptibility, production of extrapolymeric material and differential expression of genes in a phase dependent manner. Interaction with competitive bacterial species and its own metabolites revealed the Importance of the complex cell-to-cell signalling molecules in controlling A. fumigatus growth and biofilm development.
CONCLUSIONS: The biofilm model system complements other methods currently used to study A. fumigatus, providing an alternative method to study this fungus in a sessile growth mode. The specific consideration of A. fumigatus as a biofilm with phase dependency has provided unique insights into potential novel markers of infection and alternative treatment options which may help prevent biofilm development and invasive disease.
| Date of Award | 2008 |
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| Original language | English |
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| Supervisor | Gordon Ramage (Supervisor) |