Saccharomyces cerevisiae S288c
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318556 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Invasive fungal infections (IFIs) are difficult to treat. Few effective antifungal drugs are available and many have problems with toxicity, efficacy and drug-resistance. To overcome these challenges, existing therapies may be enhanced using more than one agent acting in synergy. Previously, we have found amphotericin B (AMB) and the iron chelator, lactoferrin (LF), were synergistic against Cryptococcus neoformans and Saccharomyces cerevisiae. This study investigates the mechanism of AMB+LF synergy, using RNA-seq and network analyses. Genes involved in iron homeostasis showed increased expression upon treatment with AMB alone. Unexpectedly, AMB+LF treatment did not lead to increased expression of iron or zinc homeostasis genes however we observed decreased expression of oxidative stress response genes. Addition of iron or zinc to AMB+LF treated cells did not rescue the synergy, supporting the likelihood that the mechanism of synergy involves more than iron and zinc chelation. We clustered genes based on patterns of co-expression and found by network analysis that many genes involved in iron and zinc homeostasis, which have dysregulated expression upon AMB+LF treatment, are targets of transcription factors Aft1p and Zap1p. Hypothesizing that these might play a key role in the synergistic response, knock-out mutants of Aft1 and Zap1 were tested for increased sensitivity to AMB and oxidative stress. Both mutants showed hypersensitivity towards these treatments. Our results suggest the mechanism of AMB+LF synergy involves disruption to oxidative stress response, in addition to chelation of iron and zinc. Since Zap1 is conserved in C. neoformans and contains a putative drug binding domain, we suggest novel Zap1 binding molecules could be combined with existing antifungals to serve as synergistic antifungal treatments for this species.
2016-12-04 | GSE80357 | GEO
Project description:Invasive fungal infections (IFIs) are difficult to treat. Few effective antifungal drugs are available and many have problems with toxicity, efficacy and drug-resistance. To overcome these challenges, existing therapies may be enhanced using more than one agent acting in synergy. Previously, we have found amphotericin B (AMB) and the iron chelator, lactoferrin (LF), were synergistic against Cryptococcus neoformans and Saccharomyces cerevisiae. This study investigates the mechanism of AMB+LF synergy using RNA-seq in Cryptococcus neoformans H99.
2019-09-08 | GSE130375 | GEO
Project description:Transcriptome and network analyses in Saccharomyces cerevisiae reveal that amphotericin B and lactoferrin synergy disrupt metal homeostasis and stress response
| PRJNA318684 | ENA
Project description:Transcriptomics analysis of amphotericin B and lactoferrin drug synergy in Cryptococcus neoformans H99
| PRJNA539938 | ENA
Project description:The iron-binding glycoprotein lactoferrin exhibits anti-bacterial activity. To investigate the overall response of Bacillus cereus to lactoferrin, total transcriptome analyses were performed. Growth conditions were mMOD minimal medium, minimal medium plus 10 mg/ml lactoferrin, as well as minimal medium without iron source for comparison. Differential regulation of genes involved in iron acquisition as well as genes encoding enterotoxins and further virulence factors was of special interest.
2023-10-01 | GSE241250 | GEO
Project description:The Saccharomyces cerevisiae gene PIF1 encodes a conserved eukaryotic DNA helicase required for both mitochondrial and nuclear DNA integrity. Our previous work revealed that a pif1D strain is tolerant to zinc overload. We demonstrate here that this effect is independent of the Pif1 helicase activity and is only observed when the protein is absent from the mitochondria. pif1 cells accumulate abnormal amounts of mitochondrial zinc and iron. Transcriptional profiling reveals that pif1 cells under standard growth conditions overexpress aconitase-related genes. When exposed to zinc, pif1 cells show lower induction of genes encoding iron (siderophores) transporters and higher expression of genes related to oxidative stress responses than wild type cells. Coincidently, pif1 mutants are less prone to zinc-induced oxidative stress and display a higher reduced/oxidized glutathione ratio. Strikingly, although pif1 cells contain normal amounts of the Aco1 protein, they completely lack aconitase activity. Loss of Aco1 activity is also observed when the cell expresses a non-mitochondrially targeted form of Pif1. We postulate that lack of Pif1 forces aconitase to play its DNA protective role as nucleoid protein and that this would trigger a domino effect on iron homeostasis resulting in increased zinc tolerance.
2010-06-01 | GSE18411 | GEO
Project description:Elucidation of molecular basis of Iron and zinc homeostasis is crucial to breed iron and zinc use efficient and iron -zinc biofortified maize cultivars. The present investigation was framed to decipher the global expression snapshot maize seedlings in response to iron and zinc starvtion. Genome-wide transcriptome assay was performed with ~18,000 transcripts distributed across the maize genome, in maize seedlings after exposing the seedlings to three Fe and Zn stress treatments (+Fe–Zn, –Fe+Zn, –Fe–Zn) along with control (+Fe+Zn). Microarrays were used to study the global gene expression pattern iron and zinc starvation responsive genes in maize.
2021-01-04 | GSE122581 | GEO
Project description:Lactoferrin is a highly multifunctional protein. Indeed, it is involved in many physiological functions, including regulation of iron absorption and immune responses. We use microarrays to study the global genome expression of C. elegans fed with a nutraceutical product based on encapsulated lactoferrin.
2017-06-12 | GSE71482 | GEO
Project description:The Saccharomyces cerevisiae gene PIF1 encodes a conserved eukaryotic DNA helicase required for both mitochondrial and nuclear DNA integrity. Our previous work revealed that a pif1D strain is tolerant to zinc overload. We demonstrate here that this effect is independent of the Pif1 helicase activity and is only observed when the protein is absent from the mitochondria. pif1 cells accumulate abnormal amounts of mitochondrial zinc and iron. Transcriptional profiling reveals that pif1 cells under standard growth conditions overexpress aconitase-related genes. When exposed to zinc, pif1 cells show lower induction of genes encoding iron (siderophores) transporters and higher expression of genes related to oxidative stress responses than wild type cells. Coincidently, pif1 mutants are less prone to zinc-induced oxidative stress and display a higher reduced/oxidized glutathione ratio. Strikingly, although pif1 cells contain normal amounts of the Aco1 protein, they completely lack aconitase activity. Loss of Aco1 activity is also observed when the cell expresses a non-mitochondrially targeted form of Pif1. We postulate that lack of Pif1 forces aconitase to play its DNA protective role as nucleoid protein and that this would trigger a domino effect on iron homeostasis resulting in increased zinc tolerance. Four samples were analyzed: WT and pif1 mutant both, in the presence and in the absence of 5 mM ZnCl2 for 1 h. We compared the expression profile of: 1) WT+Zn vs WT-Zn, 2) pif1 mutant+Zn vs pif1 mutant-Zn, 3) pif1 mutant vs WT, and 4) pif1 mutant+Zn vs WT+Zn. A Dye-swap was carried out for each comparison of samples. Total number of chips analyzed: 8.
2010-05-31 | E-GEOD-18411 | biostudies-arrayexpress
Project description:Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and neutrophils in mammals. In this study, we created a mouse model of lipopolysaccharide (LPS)-induced acute lung injury and explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in acute lung injury using the RNA sequencing (RNA-seq) technology and transcriptome analysis.
2023-12-19 | GSE247266 | GEO