The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in Aspergillus fumigatus .
Tamás EmriKároly AntalKinga VargaBarnabás Csaba GilaIstván PócsiPublished in: Journal of fungi (Basel, Switzerland) (2024)
Pathogens have to cope with oxidative, iron- and carbon(glucose)-limitation stresses in the human body. To understand how combined iron-carbon limitation alters oxidative stress responses, Aspergillus fumigatus was cultured in glucose-peptone or peptone containing media supplemented or not with deferiprone as an iron chelator. Changes in the transcriptome in these cultures were recorded after H 2 O 2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes, only the cat2 catalase-peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless of culturing conditions in oxidative stress protection, while the enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g., iron availability or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy.
Keyphrases
- oxidative stress
- iron deficiency
- induced apoptosis
- dna damage
- blood glucose
- endothelial cells
- ischemia reperfusion injury
- gene expression
- diabetic rats
- genome wide
- metabolic syndrome
- stem cells
- risk assessment
- type diabetes
- transcription factor
- candida albicans
- multidrug resistant
- signaling pathway
- copy number
- hydrogen peroxide
- rna seq
- insulin resistance
- smoking cessation
- gram negative
- genome wide identification
- combination therapy
- pi k akt
- cell cycle arrest
- glycemic control
- anti inflammatory