The characteristics of Aspergillus fumigatus mycetoma development: is this a biofilm?

Aspergillus fumigatus is an increasingly prevalent opportunistic fungal pathogen of various immuno-compromised individuals. It has the ability to filament within the lungs forming dense intertwined mycelial balls. These morphological characteristics resemble those of microbial biofilms, which are matrix enclosed microbial populations, adherent to each other and/or to surfaces or interfaces. The purpose of this paper is to review some recent experiments that indicate the potential biofilm forming capacity of A. fumigatus in vitro. Initially it was established that conidial seeding density is important for stable biofilm development. In the optimized model conidial germination and filamentous growth characteristics were not observed until 8 h, after which a multi-cellular population expanded exponentially forming a thick structure (approx. 250 microm). Calcofluor white staining of this revealed the presence of extracellular polymeric matrix material, which increased as the biofilm matured. Subsequent antifungal sensitivity testing of this structure showed that azoles, polyenes and echinocandins were ineffective in reducing the cellular viability at therapeutically attainable concentrations. Microarray and real-time PCR analysis demonstrated the up-regulation of AfuMDR4 during multicellular growth and development, which may account the recalcitrance observed. Overall, A. fumigatus appears to possess the classical elements of biofilm growth, namely multicellularity, matrix production and sessile resistance. This controversial approach to understanding the biology of A. fumigatus infection may provide crucial information on how to treat this pathogenic fungus more effectively.