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

Arite Bigalke
Axel A. Brakhage
Simone Edenhart
Katherine Gonzalez Rojas
Melanie Händel
Thorsten Heinekamp
Isabel Heineking
Nico Hermsdorf
Leijie Jia
Moemi Kawashima
Olaf Kniemeyer
Maximilian Knott
Thomas Krüger
Liubov Nikitashina
Muhammad Rafiq
Franziska Schmidt
Silke Steinbach
Eric Unger
Corissa Visser
Kerren Volkmar
Rasha Zaher
Ann-Kathrin Zimmermann

Publications

Dellière S, Chauvin C, Wong SSW, Gressler M, Possetti V, Parente R, Fontaine T, Krüger T, Kniemeyer O, Bayry J, Carvalho A, Brakhage AA, Inforzato A, Latgé JP, Aimanianda V (2024) Interplay between host humoral pattern recognition molecules controls undue immuneresponses against Aspergillus fumigatus. Nat Commun 15(1), 6966.
Guenther K, Nischang V, Cseresnyés Z, Thomas T, Sheta D, Abboud Z, Heinekamp T, Werner M, Kniemeyer O, Beilhack A, Figge MT, Brakhage A, Werz O#, Jordan P# (2024) Aspergillus fumigatus-derived gliotoxin impacts innate immune cell activation through modulating lipid mediator production in macrophages. Immunology [Epub ahead of print]
Jia LJ#, González K*, Orasch T*, Schmidt F*, Brakhage AA# (2024) Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities. Nat Microbiol 9(9), 2216-2231. (Review)
Pinzan CF, Valero C, de Castro PA, da Silva JL, Earle K, Liu H, Horta MAC, Kniemeyer O, Krüger T, Pschibul A, Cömert DN, Heinekamp T, Brakhage AA, Steenwyk JL, Mead ME, Hermsdorf N, Filler SG, da Rosa-Garzon NG, Delbaje E, Bromley MJ, Cabral H, Diehl C, Angeli CB, Palmisano G, Ibrahim AS, Rinker DC, Sauters TJC, Steffen K, Gumilang A, Rokas A, Gago S, Dos Reis TF, Goldman GH (2024) Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation. Nat Microbiol [Epub ahead of print]
van Rhijn N, Zhao C, Al-Furaji N, Storer ISR, Valero C, Gago S, Chown H, Baldin C, Grant RF, Bin Shuraym H, Ivanova L, Kniemeyer O, Krüger T, Bignell E, Goldman GH, Amich J, Delneri D, Bowyer P, Brakhage AA, Haas H, Bromley MJ (2024) Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging. Nat Commun 15(1), 4984.
Bigalke A, Krüger T, Jia LJ, Kniemeyer O, Brakhage AA (2023) Pathoproteomik des humanpathogenen Pilzes Aspergillus fumigatus. BIOspektrum (3), 269-272.
Garloff V, Krüger T, Brakhage A, Rubio I (2023) Control of TurboID-dependent biotinylation intensity in proximity ligation screens. J Proteomics 279, 104886.
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# (2023) Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway. Cell Host Microbe 31(3), 373-388.e10.
Krespach MKC, Stroe MC, Netzker T, Rosin M, Zehner LM, Komor AJ, Beilmann JM, Krüger T, Scherlach K, Kniemeyer O, Schroeckh V, Hertweck C, Brakhage AA (2023) Streptomyces polyketides mediate bacteria-fungi interactions across soil environments. Nat Microbiol 8(7), 1348-1361.
Mirhakkak MH*, Chen X*, Heinekamp T, Sae-Ong T, Xu LL, Ni Y, Kurzai O, Barber AE, Brakhage AA, Boutin S, Schäuble S#, Panagiotou G# (2023) Genome-scale Metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome. Nat Commun 14(1), 4369.