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SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus.

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Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs in the human fungal pathogens Cryptococcus neoformans and

Functional analysis of selected deletion mutants in Candida glabrata under hypoxia.

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Increased drug resistance in Candida glabrata (a model non-albicans Candida) calls for the identification of potential molecular targets for the development of effective drugs. Hypoxia (a state of low oxygen) is an important host factor, which affects the virulence of the pathogen and efficacy of

Exometabolome analysis reveals hypoxia at the up-scaling of a Saccharomyces cerevisiae high-cell density fed-batch biopharmaceutical process.

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BACKGROUND Scale-up to industrial production level of a fermentation process occurs after optimization at small scale, a critical transition for successful technology transfer and commercialization of a product of interest. At the large scale a number of important bioprocess engineering problems

[The effect of oxygen deficiency on the stability of the yeast Saccharomyces cerevisiae to the polyenic antibiotic nystatin].

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Oxygen deficiency was shown to affect the resistance of different Saccharomyces cerevisiae strains to nystatin, a polyenic antibiotic. This resistance decreased upon oxygen deficiency in the wild-type strains alpha'1 and 7A-P192 as well as in the mutant strains NYS 2, NYS 3 and NYS 4, but remained

Two C4-sterol methyl oxidases (Erg25) catalyse ergosterol intermediate demethylation and impact environmental stress adaptation in Aspergillus fumigatus.

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The human pathogen Aspergillus fumigatus adapts to stress encountered in the mammalian host as part of its ability to cause disease. The transcription factor SrbA plays a significant role in this process by regulating genes involved in hypoxia and low-iron adaptation, antifungal drug responses and

Coordination of hypoxia adaptation and iron homeostasis in human pathogenic fungi.

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In mammals, hypoxia causes facilitated erythropoiesis that requires increased iron availability with established links between oxygen and iron in regulation of the transcription factor hypoxia-inducible factor. Therefore, cellular responses to hypoxia and iron starvation are linked in mammals and

Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans.

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We investigated the effects of the hypoxia-mimetic CoCl2 in the pathogenic fungus Cryptococcus neoformans and demonstrated that CoCl2 leads to defects in several enzymatic steps in ergosterol biosynthesis. Sterol defects were amplified in cells lacking components of the Sre1p-mediated oxygen-sensing

Effects of culture conditions on ergosterol biosynthesis by Saccharomyces cerevisiae.

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Ergosterol is an essential component of yeast cells that maintains the integrity of the membrane. It was investigated as an important factor in the ethanol tolerance of yeast cells. We investigated the effects of brewing conditions on the ergosterol contents of S. cerevisiae K-9, sake yeast, several

Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter.

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BACKGROUND Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of

A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus.

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At the site of microbial infections, the significant influx of immune effector cells and the necrosis of tissue by the invading pathogen generate hypoxic microenvironments in which both the pathogen and host cells must survive. Currently, whether hypoxia adaptation is an important virulence

Large-scale transcriptional response to hypoxia in Aspergillus fumigatus observed using RNAseq identifies a novel hypoxia regulated ncRNA.

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We utilized RNAseq analysis of the Aspergillus fumigatus response to early hypoxic condition exposure. The results show that more than 89% of the A. fumigatus genome is expressed under normoxic and hypoxic conditions. Replicate samples were highly reproducible; however, comparisons between normoxia

Ergosterol Attenuates Isoproterenol-Induced Myocardial Cardiotoxicity.

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Phytomedicine has shown a promising potential for the prevention of cardiovascular system diseases and disorders. This study aimed to evaluate protective effect of ergosterol (ER) on isoproterenol (ISO)-induced myocardial cardiotoxicity. We found that pretreatment with ER significantly decreased

Hypoxia: A Double-Edged Sword During Fungal Pathogenesis?

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Molecular oxygen functions as an electron acceptor for aerobic respiration and a substrate for key metabolisms and cellular processes. Most eukaryotes develop direct or indirect oxygen sensors and reprogram transcriptional and translational metabolisms to adapt to altered oxygen availability under

Ergosterol regulates sterol regulatory element binding protein (SREBP) cleavage in fission yeast.

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In fission yeast, the endoplasmic reticulum membrane-bound proteins Sre1 and Scp1, orthologs of mammalian sterol regulatory element binding protein (SREBP) and Scap, monitor sterol synthesis as an indirect measure of oxygen supply. When cellular oxygen levels are low, sterol synthesis is inhibited,

ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence.

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The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete

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