The filamentous fungal genus Aspergillus includes several species, which have attained prominence in human affairs. On the positive side, Aspergillus spp. play a significant role as ’’cell factories’’ in the field of white biotechnology. On the negative side, however, Aspergillus spp. can cause superficial and severe invasive infections in animals and humans. Among the Aspergillus spp., Aspergillus fumigatus has become the most prevalent airborne fungal pathogen, which is able to cause life-threatening invasive aspergillosis (IA) in immunocompromised patients (e. g. transplant and chemotherapy patients). It is still unclear why among the filamentous fungi A. fumigatus is the pre-dominant pathogen causing IA. The current release of the genome sequences of A. fumigatus and other Aspergillus spp. has opened the way for global analyses of protein expression in Aspergilli including the characterisation of virulence traits, which support survival and growth in the human host. We are studying the fitness attributes of A. fumigatus which confer resistance to the adverse environmental conditions in the host by combining proteome profiling and molecular biology. In a first step, we established 2-D gel reference maps for mycelial and conidial proteins of A. fumigatus: In mycelium, particularly proteins involved in cellular metabolism, protein synthesis, transport processes and cell cycle were high abundant and were detected and identified in 2D-gels. In comparison, dormant conidia showed an over-representation of proteins involved in detoxification of reactive oxygen species (ROS), formation of pigments and assembly of the conidial surface layer. These proteins most probably account for the enormous stress resistance of dormant conidia. Enzymes mediating resistance against ROI are also secreted into the culture supernatant by A. fumigatus. Noteworthy even during growth on glucose, A. fumigatus secretes a large number of proteases and a considerable number of glycoside hydrolases that are required for the utilisation of plant-derived polysaccharides. Investigation of the proteomic response of A. fumigatus to stress conditions, which are relevant to host infection, such as oxidative stress, elevated temperatures and hypoxia revealed the following: Upon exposure to hydrogen peroxide, besides catalases, especially proteins of the thioredoxin system were induced. Thus, they may play an important role in redox regulation in A. fumigatus. A proteomic survey of the heat shock response provided evidence for the a regulation of mannitol biosynthesis, translation, cytoskeletal dynamics and cell division by the heat shock transcription factor Hsf1. Quite surprisingly, adaptation to hypoxia was associated with an increase in the level of respiratory proteins and the production of the secondary metabolite pseurotin A. It is interesting to speculate that the observed stimulation of the biosynthesis of a secondary metabolite by hypoxia may also affect the survival of A. fumigatus during the infection when oxygen levels decline. Further genetic studies will try to elucidate the role of stress-induced proteins in counteracting immune defences. Altogether, exciting insights into the A. fumigatus physiology, stress response and pathogenicity have already been gained by proteomic studies. Nevertheless, proteomic techniques are still not able to depict completely the proteome of an eukaryotic organism like A. fumigatus. Technical improvements, however, will probably lead to the development of more sensitive and reliable methods.
Full conference title:
Trends in Medical Mycology, 5th
- TIMM 5th (2013)