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

Publications

Brakhage AA (2024) Microbial hub signaling compounds: natural products disproportionally shape microbiome composition and structure. microLife 5, uqae017.
Brakhage AA, Kniemeyer O, Zipfel PF (2024) Human and animal relationships. In: Brakhage AA, Kniemeyer O, Zipfel PF (eds.) The Mycota - Human and animal relationships. 3. 6, pp. vii-viii. Springer, Cham. ISBN: 978-3-031-64853. (Review)
Delbaje E, de Castro PA, Calise DG, Mengyao N, Horta MAC, Akiyama DY, Pontes JG, Fill T, Kniemeyer O, Krüger T, Brakhage AA, Wong KH, Keller NP, Goldman GH (2024) The influence of Aspergillus fumigatus fatty acid oxygenases PpoA and PpoC on Caspofungin susceptibility. J Fungi 10(11), 749.
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.
Ghandour R, Devlitsarov D, Popp P, Melamed S, Huber M, Siemers M, Krüger T, Kniemeyer O, Klingl A, Brakhage AA, Erhardt M, Papenfort K (2024) ProQ-associated small RNAs control motility in Vibrio cholerae. Nucleic Acids Res gkae1283, 1-19.
Günther K, Nischang V, Cseresnyés Z, Krüger T, Sheta D, Abboud Z, Heinekamp T, Werner M, Kniemeyer O, Beilhack A, Figge MT, Brakhage AA, Werz O#, Jordan PM# (2024) Aspergillus fumigatus-derived gliotoxin impacts innate immune cell activation through modulating lipid mediator production in macrophages. Immunology 173(4), 748-767.
Jia LJ, Brakhage AA# (2024) Extracellular proteins and their roles in Aspergillus fumigatus pathogenesis. In: Brakhage AA, Kniemeyer O, Zipfel PF (eds.) The Mycota - Human and Animal Relationships 3. 6, pp. 67-89. Springer, Cham. ISBN: 978-3-031-64853. (Review)
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)
König S, Schroeder J, Heinekamp T, Brakhage AA, Löffler B, Engert B, Ehrhardt C (2024) ProcCluster® and procaine hydrochloride inhibit the growth of Aspergillus species and exert antimicrobial properties during coinfection with influenza A viruses and A. fumigatus in vitro. Front Cell Infect Microbiol 14, 1445428.
Krüger T*, Kniemeyer O* (2024) Proteomics and its application to the human pathogenic fungus Aspergillus fumigatus. In: Brakhage AA, Kniemeyer O, Zipfel PF (eds.) The Mycota - Human and Animal Relationships 3. 6, pp. 227-269. Springer, Cham. ISBN: 9783031648526. (Review)