Johannes Wagener
Web: Research Support System Profile
Invasive fungal infections (IFIs) in humans are associated with high mortality rates. Especially severely immunocompromised individuals are at risk. Candida and Aspergillus species are the most important causes of IFI in Europe. The main reasons for the often fatal outcome of these infections are late diagnosis, limited treatment options and antifungal resistance.
Our research is directed towards better understanding, diagnosing, and treating diseases caused by fungal pathogens. In addition, we evaluate novel diagnostics for fungal, bacterial, viral and parasitic infections.
Research themes:
I. Antifungal drugs: mechanisms of action and resistance
The outcome of invasive fungal infections significantly depends on effective antifungal treatment. Unfortunately, only a small number of clinically approved antifungal drugs is available to treat IFIs. We study the mechanisms how these antifungals act against different fungal pathogens, and how pathogens develop resistance.
Selected publications:
- Loiko et al. The paradoxical effect of echinocandins in Aspergillus fumigatus relies on recovery of the β-1,3-glucan synthase Fks1. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01690-16.
- Geißel et al. Azole-induced cell wall carbohydrate patches kill Aspergillus fumigatus. Nat Commun. 2018 Aug 6;9(1):3098.
- Sturm et al. Differentially regulated transcription factors and ABC transporters in a mitochondrial dynamics mutant can alter azole susceptibility of Aspergillus fumigatus. Front Microbiol. 2020 May 26;11:1017.
II. Host-pathogen interaction: innate defence mechanisms and pathogenicity of Aspergillus fumigatus
The innate immune system plays a key role in the defence against invasive IFIs. The mechanisms how innate immune cells detect and kill Aspergillus hyphae and especially how Aspergillus copes with such stress remain largely uncharacterized. We recently developed a novel microscopic assay which allows us to study the antifungal activity of immune cells against Aspergillus hyphae. Our aim is to identify and characterize factors on the host and pathogen side that determine the efficacy of the host’s immune system against the pathogen to disclose novel therapeutic approaches for the treatment of IFIs.
Selected publications:
- Dichtl et al. Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases. Mol Microbiol. 2012 Feb;83(3):506-19.
- Ruf et al. Mitochondrial fragmentation in Aspergillus fumigatus as early marker of granulocyte killing activity. Front Cell Infect Microbiol. 2018 May 14;8:128.
- Brantl et al. Peroxiredoxin Asp f3 is essential for Aspergillus fumigatus to overcome iron limitation during infection. mBio. 2021 Aug 31;12(4):e0097621.
III. Clinical research: evaluation of new diagnostic tests and procedures
There is a continuous need for new diagnostic tools for timely diagnosis of infectious diseases which significantly impact the clinical management, for example, administration of therapy and interruption of transmission. To estimate the clinical value of a diagnostic test, it is essential to determine its exact properties. We systematically analyse and compare the properties of new diagnostic tests by evaluating their test characteristics with defined clinical samples.
Selected publications:
- Dichtl et al. Serological biomarkers of candidemia: a retrospective evaluation of three assays. Infection. 2019 Apr;47(2):217-224. doi: 10.1007/s15010-018-1224-3.
- Forster et al., β-1,3-D-glucan and galactomannan as biomarkers for the detection of invasive Geotrichum and Magnusiomyces infections: a retrospective evaluation. J Clin Microbiol. 2021 Oct 20:JCM0160721. doi: 10.1128/JCM.01607-21. Online ahead of print.