Pathobiology of Aspergillus fumigatus and novel strategies for the therapy of infections: Immune evasion and host-pathogen interaction as well as extracellular vesicles

Within the last decades, a rapid increase in systemic fungal infections has been observed, especially due to the increase in the number of immunosuppressed patients. More than 90 % of invasive mycoses caused by Aspergilli can be traced back to an infection with Aspergillus fumigatus. The MAM department focuses on two aspects: (1) the identification of virulence determinants of the fungus and (2) the elucidation of the interaction between A. fumigatus and the immune system, in particular neutrophil granulocytes, macrophages, epithelial and T cells. Of particular importance are immune evasion mechanisms, such as the ability of the fungus to protect itself from recognition by immune cells with the help of its surface proteins or to influence the intracellular processing of spores (conidia) with the help of its surface DHN melanin layer. This is done, for example, by inhibiting the acidification of phagolysosomes through inhibition of the formation of lipid raft microdomains in the phagolysosomal membrane or by inhibiting apoptosis. A new aspect is the discovery of extracellular vesicles formed by neutrophil granulocytes that kill the fungus.

The department is focusing on the following aspects.

  • Identification of virulence determinants of A. fumigatus
  • Elucidation of the interaction between the fungi and the immune system, in particular neutrophil granulocytes, macrophages and epithelial cells and their extracellular vesicles
  • The importance of the lung microbiome for disease development
  • New strategies for the diagnosis and therapy of Aspergillus infections
  • Development of proteomic methods for the analysis of host-pathogen interaction and microbial communities

Staff

Hanan Alderzy
Arite Bigalke
Axel A. Brakhage
Simone Edenhart
Katherine Gonzalez Rojas
Thorsten Heinekamp
Isabel Heineking
Lia Ivanova
Leijie Jia
Moemi Kawashima
Olaf Kniemeyer
Thomas Krüger
Liubov Nikitashina
Thomas Orasch
Lukáš Radosa
Muhammad Rafiq
Flora Rivieccio
Franziska Schmidt
Jeany Söhnlein
Silke Steinbach
Corissa Visser
Natascha Wilker
Ann-Kathrin Zimmermann

Publications

Balkenhol J, Bencurova E, Gupta SK, Schmidt H, Heinekamp T, Brakhage AA, Pottikkadavath A, Dandekar T (2022) Prediction and validation of host-pathogen interactions by a versatile inference approach using Aspergillus fumigatus as a case study. Comput Struct Biotechnol J 20, 4225-4237.
Brandt P, Gerwien F, Wagner L, Krüger T, Ramírez-Zavala B, Mirhakkak MH, Schäuble S, Kniemeyer O, Panagiotou G, Brakhage AA, Morschhäuser J, Vylkova S (2022) Candida albicans SR-like protein kinases regulate different cellular processes: Sky1 is involved in control of ion homeostasis, while Sky2 is important for dipeptide utilization. Front Cell Infect Microbiol 12, 850531.
Jia LJ, Rafiq M, Radosa L, Hortschansky P, Cunha C, Cseresnyés Z, Krüger T, Schmidt F, Heinekamp T, Straßburger M, Loeffler B, Doenst T, Lacerda JF, Campos A, Figge MT, Carvalho A, Kniemeyer O, Brakhage AA (2022) Re-direction of phagosomes to the recycling expulsion pathway by a fungal pathogen. bioRxiv [Preprint]
Tappe B, Lauruschkat C, Strobel L, Garcia JP, Kurzai O, Rebhan S, Kraus S,Tappe B, Lauruschkat C, Strobel L, Garcia JP,, Bussemer L, Possler L, Held M, Huenniger K, Kniemeyer O, Schaeuble S, Brakhage A, Panagiotou G, White L, Einsele H, Löffler J, Wurster S (2022) COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds. Front Immunol 13, 954985.