PROTEOME ANALYSIS FOR PATHOGENICITY AND NEW DIAGNOSTIC MARKERS

Kniemeyer O, Leßing F, Schmidt A, Teutschbein J, Winkler R, Haas H, Brakhage

Author address: 

1Department of Molecular and Applied Microbiology and 2Department of Biostructure

Abstract: 

With the completion of the Aspergillus fumigatus genome it is now possible to study protein regulation on a global scale. One of the most successful protein separation techniques is based on 2D-gel electrophoresis, in which proteins are separated by charge and size in a gel matrix. With the application of proteomic tools it is possible to gain a comprehensive overview about the proteins of A. fumigatus present or induced during environmental changes and stress conditions. During the infection process A. fumigatus has to cope with dramatic changes of the environmental conditions. Since A. fumigatus is the most prevalent airborne fungal pathogen the question arises: Does A. fumigatus possess superior adaptation strategies in comparison to other filamentous fungi? Therefore, we analysed the proteomes of A. fumigatus grown under heat stress, oxidative stress and iron depletion. During a temperature shift from 30 °C to 48 °C many stress and heat shock proteins were up-regulated. Oxidative stress induced the up-regulation of catalases, thioredoxin peroxidase and other proteins. Under iron depletion, proteins involved in siderophore biosynthesis were up-regulated, whereas iron cluster-containing proteins were down-regulated. Some of the gene products expressed under stress responses are also known fungal antigens, such as the heat shock proteins HSP 90 or the thioredoxin peroxidase AspF3. So besides pathogenicity studies, proteomics also provides tools to screen for new antigens, which could improve the diagnosis of diseases caused by A. fumigatus infections. Culture-independent clinical tests are of great interest, since there is still no sensitive, quick and unambiguous diagnostic tool available for the detection of invasive aspergillosis.. In combination with subcellular fractionation strategies immunoproteomics is an excellent tool for the screening of new Aspergillus antigens. A tool often applied for this purpose is the combination of 2D-PAGE with immunoblotting. Besides diagnosis, fungal antigens have also a great potential for the development of vaccinations against invasive mycoses.
2008

abstract No: 

203

Full conference title: 

3rd Advances Against Aspergillosis
    • AAA 3rd (2008)