Human-like Biofilm Models to Study the Activity of Antifungals Against Aspergillus fumigatus

<i>Aspergillus fumigatus</i> is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host's immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by <i>A. fumigatus</i> increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against <i>A. fumigatus</i>. In both assays, metabolically active <i>A. fumigatus</i> biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against <i>Aspergillus</i> biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings.