ABSTRACT
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 H2O2 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.
ABSTRACT
The genome of the osmophilic Aspergillus wentii, unlike that of the osmotolerant Aspergillus nidulans, contains only the gfdA, but not the gfdB, glycerol 3-phosphate dehydrogenase gene. Here, we studied transcriptomic changes of A. nidulans (reference strain and ΔgfdB gene deletion mutant) and A. wentii (reference strain and An-gfdB expressing mutant) elicited by high osmolarity. A. nidulans showed a canonic hyperosmotic stress response characterized by the upregulation of the trehalose and glycerol metabolism genes (including gfdB), as well as the genes of the high-osmolarity glycerol (HOG) map kinase pathway. The deletion of gfdB caused only negligible alterations in the transcriptome, suggesting that the glycerol metabolism was flexible enough to compensate for the missing GfdB activity in this species. A. wentii responded differently to increased osmolarity than did A. nidulans, e.g., the bulk upregulation of the glycerol and trehalose metabolism genes, along with the HOG pathway genes, was not detected. The expression of An-gfdB in A. wentii did not abolish osmophily, but it reduced growth and caused much bigger alterations in the transcriptome than did the missing gfdB gene in A. nidulans. Flexible glycerol metabolism and hence, two differently regulated gfd genes, may be more beneficial for osmotolerant (living under changing osmolarity) than for osmophilic (living under constantly high osmolarity) species.
ABSTRACT
Although tyrosol is a quorum-sensing molecule of Candida species, it has antifungal activity at supraphysiological concentrations. Here, we studied the effect of tyrosol on the physiology and genome-wide transcription of Aspergillus nidulans to gain insight into the background of the antifungal activity of this compound. Tyrosol efficiently reduced germination of conidia and the growth on various carbon sources at a concentration of 35 mM. The growth inhibition was fungistatic rather than fungicide on glucose and was accompanied with downregulation of 2199 genes related to e.g. mitotic cell cycle, glycolysis, nitrate and sulphate assimilation, chitin biosynthesis, and upregulation of 2250 genes involved in e.g. lipid catabolism, amino acid degradation and lactose utilization. Tyrosol treatment also upregulated genes encoding glutathione-S-transferases (GSTs), increased specific GST activities and the glutathione (GSH) content of the cells, suggesting that A. nidulans can detoxify tyrosol in a GSH-dependent manner even though this process was weak. Tyrosol did not induce oxidative stress in this species, but upregulated "response to nutrient levels", "regulation of nitrogen utilization", "carbon catabolite activation of transcription" and "autophagy" genes. Tyrosol may have disturbed the regulation and orchestration of cellular metabolism, leading to impaired use of nutrients, which resulted in growth reduction.
Subject(s)
Antifungal Agents , Aspergillus nidulans , Phenylethyl Alcohol/analogs & derivatives , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Transcriptome , Glutathione/genetics , Glutathione/metabolism , Glutathione/pharmacology , Carbon/metabolism , Gene Expression Regulation, Fungal , Fungal Proteins/genetics , Fungal Proteins/metabolismABSTRACT
Mycotoxins produced by Fusarium species are secondary metabolites with low molecular weight formed by filamentous fungi generally resistant to different environmental factors and, therefore, undergo slow degradation. Contamination by Fusarium mycotoxins in cereals and millets is the foremost quality challenge the food and feed industry faces across the globe. Several types of chemical preservatives are employed in the mitigation process of these mycotoxins, and they help in long-term storage; however, chemical preservatives can be used only to some extent, so the complete elimination of toxins from foods is still a herculean task. The growing demand for green-labeled food drives to evade the use of chemicals in the production processes is getting much demand. Thus, the biocontrol of food toxins is important in the developing food sector. Fusarium mycotoxins are world-spread contaminants naturally occurring in commodities, food, and feed. The major mycotoxins Fusarium species produce are deoxynivalenol, fumonisins, zearalenone, and T2/HT2 toxins. Lactic acid bacteria (LAB), generally regarded as safe (GRAS), is a well-explored bacterial community in food preparations and preservation for ages. Recent research suggests that LAB are the best choice for extenuating Fusarium mycotoxins. Apart from Fusarium mycotoxins, this review focuses on the latest studies on the mechanisms of how LAB effectively detoxify and remove these mycotoxins through their various bioactive molecules and background information of these molecules.