Emri Tamás, Antal Károly, Varga Kinga, Gila Barnabás Csaba, Pócsi István
Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, H-4032 Debrecen, Hungary.
HUN-REN-UD Fungal Stress Biology Research Group, H-4032 Debrecen, Hungary.
J Fungi (Basel). 2024 Mar 18;10(3):221. doi: 10.3390/jof10030221.
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, 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 HO 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 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.
病原体必须应对人体中的氧化、铁和碳(葡萄糖)限制应激。为了了解铁 - 碳联合限制如何改变氧化应激反应,在补充或不补充去铁酮(一种铁螯合剂)的葡萄糖 - 蛋白胨或含蛋白胨的培养基中培养。在过氧化氢处理后记录这些培养物中转录组的变化。对氧化应激的反应高度依赖于葡萄糖和铁的可用性。在16个应激反应性抗氧化酶基因中,只有过氧化氢酶 - 过氧化物酶基因在两种以上培养条件下上调。在这些培养物中观察到的铁代谢转录反应也有很大差异。无论培养条件如何,只有细胞外铁载体的产生在氧化应激保护中显得重要,而铁硫簇蛋白合成的增强似乎对氧化应激处理的铁限制和快速生长(富含葡萄糖)的培养物至关重要。尽管病原体和宿主细胞生活在同一位置,但它们的培养条件(例如,铁的可用性或氧化应激的发生)可能不同。因此,抑制一个普遍重要的生化过程,如铁硫簇组装,可能在体内选择性地抑制病原体生长,并代表抗真菌治疗的潜在靶点。