Fungal biofilm architecture produces hypoxic microenvironments that drive antifungal resistance
Caitlin H. Kowalski, Kaesi A. Morelli, Daniel Schultz, Carey D. Nadell, Robert A. Cramer
Abstract
Significance Failure of antimicrobial therapies to clear an infection is in part due to a biofilm mode of bacterial and fungal growth. Understanding how microbial biofilms mediate antimicrobial treatment failure is critical for improving infection outcomes. The mechanisms by which filamentous fungal biofilms mediate drug resistance are particularly ill-defined. We observe that Aspergillus fumigatus biofilms develop hypoxic microenvironments during maturation that facilitate fungal survival in the face of antifungal treatments. Oxygenation of A. fumigatus biofilms, however, reduces fungal survival. These results extend the role of dynamic biofilm oxygen gradients found in bacterial pathogens to the fungal kingdom and provide insights into how to overcome fungal drug resistance through manipulation of biofilm oxygen availability and consumption.