Engineering phagosomes in human cells as a novel anti-infection strategy

Invasive fungal infections cause life-threatening diseases with a high mortality rate worldwide, especially in people with a weakened immune system. There are currently only limited antifungal drugs available for treatment. If pathogens enter the host's tissues, the immune system is activated and fights the invaders. The process of phagocytosis is crucial for an effective immune response. In addition to the phagocytes known as "scavenger cells", epithelial cells are also able to absorb pathogens and kill them by digestion. Phagocytosis takes place in a specific intracellular structure, the phagolysosome. In recent years, however, many fungal pathogens have developed strategies to evade destruction in the phagolysosome. As a result, they can cause particularly serious diseases in humans. At the end of 2022, the WHO published the first list of human pathogenic fungi classified as extremely critical, which pose a high risk potential for humans.

The "Phagosome Biology and Engineering" research group is setting new standards in phagosome-related research. The group pursues two goals, which serve to research the interaction between fungus and host in the context of phagocytosis. One of them is to investigate the mechanisms of pathogen-induced reprogramming of phagosomes, which fungi use to avoid killing themselves in the phagolysosome of the host cells. This will also serve as a basis for the development of novel, phagosome-based anti-infective strategies. These findings could be used to develop modern technologies that could be utilized to better treat severe fungal infections.

The "Phagosome Biology and Engineering" research group is financed by the Free State of Thuringia with funds from the European Social Fund Plus (ESF+).

Staff

Isabel Heineking
Leijie Jia
Franziska Kage
Muhammad Rafiq

Publications

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). Vol. 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)

Funding

The research group "Phagosome Biology and Engineering" is financed by the Free State of Thuringia with funds from the European Social Fund Plus (ESF+).