Each year around 20% of the world’s population is affected by fungal infections resulting in excess of 1.5 million deaths. Aspergillosis accounts for around one third of deaths, which are predominantly caused by the major mold pathogen of humans Aspergillus fumigatus. The current therapeutic arsenal to treat Aspergillus infections comprises only four classes of antifungal drugs (triazoles, polyenes, echinocandins and nucleobase analogs). However, resistance to the triazoles, the major drug class administered in clinical settings, is emerging rapidly.

Our research involves the elucidation of molecular factors that contribute to antifungal activity and resistance in A. fumigatus with the overall goal to build the fundament for the development of novel therapeutic avenues. Combining a repertoire of biochemical, molecular and microbiological techniques to genetically manipulate and study this pathogenic mold, our lab aims to acquire a comprehensive understanding on the metabolic effects of antifungals as well as on the adaptive strategies employed by A. fumigatus to protect itself from antifungal compounds.

Gsaller F, Furukawa T, Carr PD, Rash B, Jochl C, Bertuzzi M, Bignell EM, Bromley MJ. Mechanistic Basis of pH-Dependent 5-Flucytosine Resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 62(6) (2018).

Misslinger M, Gsaller F, Hortschansky P, Muller C, Bracher F, Bromley MJ, Haas H. The cytochrome b5 CybE is regulated by iron availability and is crucial for azole resistance in A. fumigatus. Metallomics 9(11):1655-1665 (2017).

Gsaller F, Hortschansky P, Furukawa T, Carr PD, Rash B, Capilla J, Muller C, Bracher F, Bowyer P, Haas H, Brakhage AA, Bromley MJ. Sterol Biosynthesis and Azole Tolerance Is Governed by the Opposing Actions of SrbA and the CCAAT Binding Complex. PLoS Pathog 12(17):e1005775 (2016).

Johns A, Scharf DH, Gsaller F, Schmidt H, Heinekamp T, Strassburger M, Oliver JD, Birch M, Beckmann N, Dobb KS, Gilsenan J, Rash B, Bignell E, Brakhage AA, Bromley MJ. A Nonredundant Phosphopantetheinyl Transferase, PptA, Is a Novel Antifungal Target That Directs Secondary Metabolite, Siderophore, and Lysine Biosynthesis in Aspergillus fumigatus and Is Critical for Pathogenicity. MBio 8 (2017).

Gsaller F, Hortschansky P, Beattie SR, Klammer V, Tuppatsch K, Lechner BE, Rietzschel N, Werner ER, Vogan AA, Chung D, Muhlenhoff U, Kato M, Cramer RA, Brakhage AA, Haas H. The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess. EMBO J 33:2261-76 (2014).