Stress Responses Elicited by Glucose Withdrawal in

Glucose is a widely used carbon source in laboratory practice to culture Aspergillus fumigatus, however, glucose availability is often low in its “natural habitats”, including the human body. We used a physiological−transcriptomical approach to reveal differences between A. fumigatus Af293 cultures incubated on glucose, glucose and peptone, peptone (carbon limitation), or without any carbon source (carbon starvation). Autolytic cell wall degradation was upregulated by both carbon starvation and limitation. The importance of autolytic cell wall degradation in the adaptation to carbon stress was also highlighted by approximately 12.4% of the A. fumigatus genomes harboring duplication of genes involved in N-acetyl glucosamine utilization. Glucose withdrawal increased redox imbalance, altered both the transcription of antioxidative enzyme genes and oxidative stress tolerance, and downregulated iron acquisition, but upregulated heme protein genes. Transcriptional activity of the Gliotoxin cluster was low in all experiments, while the Fumagillin cluster showed substantial activity both on glucose and under carbon starvation, and the Hexadehydro-astechrome cluster only on glucose. We concluded that glucose withdrawal substantially modified the physiology of A. fumigatus, including processes that contribute to virulence. This may explain the challenge of predicting the in vivo behavior of A. fumigatus based on data from glucose rich cultures.