The major research focus of the Haas research group is the characterization of iron homeostasis-maintaining mechanisms of Aspergillus fumigatus, which is the most common human airborne fungal pathogen. Adaptation to iron starvation includes down-regulation of iron-consuming pathways and up-regulation of iron acquisition mechanisms, which is particularly crucial during invasive growth in the host, which represents iron limitation.
The Haas group has shown that aside from reductive iron assimilation, A. fumigatus produces extra- and intracellular siderophores for uptake, storage and intracellular distribution of iron. The transcription factors SreA, HapX and SrbA play central roles in iron regulation but several lines of evidence indicate that additional mechanisms are likely to exist. Siderophore biosynthesis, HapX and SrbA are essential for virulence of A. fumigatus as well as for other animal- and plant-pathogenic fungi, which reflects the central role of iron metabolism in fungal physiology. The recently demonstrated PET (Positron Emission Tomography) imaging of invasive pulmonary aspergillosis in a rat model, which is based on fungal accumulation of siderophore-chelated 68Gallium, stresses the potential of siderophores for the diagnosis of fungal infections.
Strong collaborations with the groups of:
Würzner, Lass-Flörl, Weiss, Marx-Ladurner
Schrettl M, Haas H. Iron homeostasis – Achilles´ heel of A. fumigatus? Curr Oppin Microbiol 14:400-405 (2011).
McDonagh A, Fedorova ND, Crabtree J, Yu Y, Kim S, Chen D, Loss O, Cairns T, Goldman G, Armstrong-James D, Haynes K, Haas H, Schrettl M, May G, Nierman WC, Bignell E. Sub-telomere directed gene expression during initiation of invasive aspergillosis. PLoS Pathog 4(9):e1000154 (2008).
Schrettl M, Bignell E, Kragl C, Sabiha Y, Loss O, Eisendle M, Wallner A, Arst HN Jr, Haynes K, Haas H. Distinct Roles for Intra- and Extracellular Siderophores during Aspergillus fumigatus Infection. PLoS Pathog 3:1195-1207 (2007).
Schrettl M, Kim HS, Eisendle M, Kragl C, Nierman WC, Heinekamp T, Werner ER, Jacobsen I, Illmer P, Yi H, Brakhage AA, Haas H. SreA-mediated iron regulation in Aspergillus fumigatus. Mol Microbiol 70:27-43 (2008).
Blatzer M, Barker BM, Willger SD, Beckmann N, Blosser SJ, Cornish EJ, Mazurie A, Grahl N, Haas H*, H Cramer R. SREBP coordinates iron and ergosterol homeostastis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus. PLoS Genetics 7(12):e1002374 (2011).
Petrik M, Haas H, Schrettl M, Helbok A, Blatzer M, Decristoforo C. In vitro and in vivo evaluation of selected 68Ga-siderophores for infection imaging. Nucl Med Biol 39:361-369 (2012).
Reinhard Würzner, M.D., Ph.D.