Antifungal Therapeutics and Resistance

Our research focuses on the molecular investigation of antifungal drug mechanisms of action and to elucidate factors that contribute to antifungal resistance. We aim to acquire a more comprehensive understanding on the metabolic effects of antifungals as well as on the adaptive strategies employed by Aspergillus fumigatus to protect itself from antifungal compounds with the final goal to develop alternative strategies to treat fungal diseases. Homepage

Topics

  • Transcriptional regulation based antifungal resistance
  • Metabolic pathways targeted by antifungal drugs
  • Novel tools facilitating genetic engineering

Projects

  • Development of novel 5-fluorocytosine based antifungal therapeutics

Technologies

  • Genetic manipulation of Aspergillus spp. (gene deletions, knock-ins, site-directed mutagenesis, conditional expression mutants)
  • Antifungal susceptibility testing (minimum-inhibitory-concentration determination, plate assay based resistance testing)
  • Gene expression analysis (reporter assays, qRT-PCR, Northern analysis)
  • Phenotypical analysis of mutant strains
  • Microscopy (multicolor fluorescence microscopy, time-lapse)

Key Publications

Furukawa T, van Rhijn N, Fraczek M, Gsaller F, Davies E, Carr P, Gago S, Fortune-Grant R, Rahman S, Gilsenan JM, Houlder E, Kowalski CH, Raj S, Paul S, Cook P, Parker JE, Kelly S, Cramer RA, Latge JP, Moye-Rowley S, Bignell E, Bowyer P, Bromley MJ. (2020). The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Nat Commun 11:427
Gsaller F, Furukawa T, Carr PD, Rash B, Jochl C, Bertuzzi M, Bignell EM, Bromley MJ. (2018). Mechanistic Basis of pH-Dependent 5-Flucytosine Resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 62
Gsaller F, Hortschansky P, Furukawa T, Carr PD, Rash B, Capilla J, Muller C, Bracher F, Bowyer P, Haas H, Brakhage AA, Bromley MJ. (2016). Sterol Biosynthesis and Azole Tolerance Is Governed by the Opposing Actions of SrbA and the CCAAT Binding Complex. PLoS Pathog 12:e1005775
 

Group Leader

Fabio Gsaller, PhD

Medical University of Innsbruck

Institute of Molecular Biology/Biocenter

Innrain 80/82, 6020 Innsbruck

+43 512 9003 70224

This email address is being protected from spambots. You need JavaScript enabled to view it.

Group Members

  • Luis-Enrique Sastre Velasquez, MSc

    PhD student; Resistance of Aspergillus fumigatus to 5-fluorocytosine; This email address is being protected from spambots. You need JavaScript enabled to view it.
  • Alexander Kühbacher, MSc

    technician; This email address is being protected from spambots. You need JavaScript enabled to view it.
  • Petra Merschak, Ing

    technician; This email address is being protected from spambots. You need JavaScript enabled to view it.
  • Mandy Peiffer, BSc

    MSc student; Reporter analysis of antifungal resistance associated genetic factors; This email address is being protected from spambots. You need JavaScript enabled to view it.