Stress Responses Elicited by Glucose Withdrawal in Aspergillus fumigatus

Abstract

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.

AcuM and AcuK: the global regulators controlling multiple cellular metabolisms in a dimorphic fungusTalaromyces marneffei

“…Importantly the use of antimycin A could exacerbate the formation of mitochondrial ROS (31). The recent study by Emri et al reveals that oxidative stress response in A. fumigatus is highly dependent on glucose and iron availability (62). Siderophore production and synthesis of Fe-S cluster proteins are crucial for cells to cope with iron limitation and oxidative stress (62).…”

“…The recent study by Emri et al reveals that oxidative stress response in A. fumigatus is highly dependent on glucose and iron availability (62). Siderophore production and synthesis of Fe-S cluster proteins are crucial for cells to cope with iron limitation and oxidative stress (62). The expression of the alternative oxidase aoxA gene is dependent on iron availability and the presence of H 2 O 2 , suggesting the role of aoxA in maintaining the redox status of mitochondria during the oxidative stress response (62).…”

“…Siderophore production and synthesis of Fe-S cluster proteins are crucial for cells to cope with iron limitation and oxidative stress (62). The expression of the alternative oxidase aoxA gene is dependent on iron availability and the presence of H 2 O 2 , suggesting the role of aoxA in maintaining the redox status of mitochondria during the oxidative stress response (62). Based on our results, we speculate that the AcuK/AcuM protein family likely participates in antioxidant mechanisms as well as other combinatorial stress responses in multiple fungi.…”

“…Importantly the use of antimycin A could exacerbate the formation of mitochondrial ROS (31). The recent study by Emri et al reveals that oxidative stress response in A. fumigatus is highly dependent on glucose and iron availability (62).…”

The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in Aspergillus fumigatus

“…Experimental data demonstrate that a stress response or the susceptibility to a stressor highly depend on culturing conditions like the type and availability of carbon sources [ 25 , 26 , 27 ], the availability of other nutrients like iron [ 23 , 28 ], or the effect of other stressors acting sequentially or concomitantly [ 29 , 30 , 31 ]. This condition dependence of stress responses may explain some of the controversial results with the importance of oxidative stress tolerance in virulence, i.e., the in vitro-identified key elements of the oxidative stress response may not be important under conditions occurring in the human body.…”