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Studies towards development of drugs targeting aspergillus fumigatus

: Seegers, Carla
: Routier, Françoise; Braun, Armin

Hannover, 2018, 65 pp.
Hannover, Medizinische Hochschule, Master Thesis, 2018
Master Thesis
Fraunhofer ITEM ()
Aspergillus fumigatus; drug development

Aspergillus fumigatus is a saprotrophic mold that is widespread all over the world and the airborne spores can be detected in high concentrations up to ~10 spores/m3. Due to this occurrence of fungal conidia, we inhale several spores every day which is harmless for people with an intact immune system. But patients suffering from immunosuppression due to AIDS/HIV, organ transplants or cancer or pre-existing lung issues, can develop a broad spectrum of Aspergillosis. Treatments with common antifungals have a low efficacy and show severe side effects like nephrotoxicity and high drug interactions. Even if combination therapies reduce these side effects, a harmless and effective antifungal treatment is still not available. One major limitation for the development of new antifungals is the lack of a representative test system for fungal infections in human. Cell lines give a good insight into the cell pathogen interactions, but lack the complexity of tissue and organ. This problem does not occur within animal but the immune response to the fungal infection is not always comparable to infections in human lung tissue. To overcome this lack of a representative test system, we started to establish an fungal ex vivo infection model with viable human lung tissue using precision-cut lung slices (PCLSs). In this work we were able to establish an infection setup with a stable fungal load and could detect a functional immune response of IL-8, IL-6 and IL-1β in the supernatant of infected PCLS. Furthermore, we could show the development of a qPCR method for the quantification of fungal load and human tissue in the infected samples. We also focussed on the establishment of a new detection method of tissue viability.