17/2009 Dr. Olaf Kniemeyer
The hypoxic (low-oxygen) response of the pathogenic mould Aspergillus fumigatus and its relevance to pathogenicity

Abstract:
Aspergillus fumigatus is an environmental mould pathogen requiring atmospheric levels of oxygen for optimal growth. Upon inhalation, A. fumigatus spores germinate, undergo hyphal growth and spread in the lungs causing deadly invasive aspergillosis in immunocompromised patients. During the infection A. fumigatus has to cope with low-oxygen microenvironments in inflammatory, necrotic tissue. Recently, it was shown that hypoxia adaptation is an important virulence attribute of A. fumigatus. Nevertheless, the knowledge about the metabolic and regulatory pathways by which A. fumigatus adapts to hypoxic condition is rather fragmentary. Recently, we performed proteomic analyses of the response of A. fumigatus to low oxygen partial pressure by using an oxygen-controlled chemostat. Many proteins of the primary metabolism, especially proteins of the mitochondrial respiratory chain, stress response and sterol biosynthesis pathway were up-regulated. In this project, the proteomic analyses will be extended to the characterisation of fractions of the mitochondrial proteome (membrane, matrix) using different proteomic methods. Interesting proteins will be selected for further characterisation by applying molecular biology techniques. Furthermore, metabolites produced during growth of A. fumigatus under hypoxic conditions will be analysed by using HPLC or GC. In short, the projects aims at ascertaining the importance of the mitochondrial metabolism during adaptation of A. fumigatus to hypoxic environments and elucidating the energy generating pathways which guarantee survival at low oxygen partial pressure.

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