Compare transcriptome profile of reference strain and mutant of HapX during A.niger grown on maltose
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ABSTRACT:
ORGANISM(S): Aspergillus niger
PROVIDER: GSE260627 | GEO | 2024/05/17
REPOSITORIES: GEO
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Project description:Iron is an essential cofactor for a wide range of cellular processes. Previous studies have shown that siderophore-mediated uptake and intracellular handling of iron are crucial for virulence of Aspergillus fumigatus. Here we show that the bzip-type transcription factor HapX plays a crucial role in the transcriptional remodeling required for adaption to iron starvation in this opportunistic fungal pathogen. HapX was found to be interconnected in a negative feed-back loop with the previously identified iron regulator SreA: SreA repressed expression of hapX during iron sufficiency and HapX repressed sreA during iron starvation. Genome-wide transcriptional profiling and analysis of selected metabolites (protophorphyrine IX, siderophores and amino acids) indicated extensive metabolic remodeling in response to iron starvation. HapX was found to participate in both, repression and activation of genes during iron starvation. HapX was in particular required for repression of iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster biosynthesis and heme biosynthesis. Pathways positively affected by HapX included production of siderophores and the ribotoxin and major allergen AspF1. Analysis of the free amino acid pool revealed HapX-dependent coordination of the production of siderophores with the supply of its precursor ornithine. Consistent with the hapX expression pattern, HapX-deficiency was deleterious with respect to growth rate and conidiation during iron depleted but not iron-replete conditions. HapX-deficiency caused significant attenuation of virulence in a murine model aspergillosis underlining that A. fumigatus faces iron starvation in the host and that the HapX-dependent metabolic reprogramming is therefore crucial for virulence. A. fumigatus 293 and hapX mutants were grown in the presence and absence of iron and in cultures shifted from no iron to iron-containing conditions after 1 h incubation. Hybridizations were performed with biological replicates for wt vs hapX +/- iron. For the iron-shift experiments, there were biological replicates for wt in both conditions and for hapX in -iron but there was only a single biological sample for hapX iron-shift sample. All hybs were performed with flip-dye pairs.
2010-07-01 | E-GEOD-22052 | biostudies-arrayexpress
Project description:Iron is an essential cofactor for a wide range of cellular processes. Previous studies have shown that siderophore-mediated uptake and intracellular handling of iron are crucial for virulence of Aspergillus fumigatus. Here we show that the bzip-type transcription factor HapX plays a crucial role in the transcriptional remodeling required for adaption to iron starvation in this opportunistic fungal pathogen. HapX was found to be interconnected in a negative feed-back loop with the previously identified iron regulator SreA: SreA repressed expression of hapX during iron sufficiency and HapX repressed sreA during iron starvation. Genome-wide transcriptional profiling and analysis of selected metabolites (protophorphyrine IX, siderophores and amino acids) indicated extensive metabolic remodeling in response to iron starvation. HapX was found to participate in both, repression and activation of genes during iron starvation. HapX was in particular required for repression of iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster biosynthesis and heme biosynthesis. Pathways positively affected by HapX included production of siderophores and the ribotoxin and major allergen AspF1. Analysis of the free amino acid pool revealed HapX-dependent coordination of the production of siderophores with the supply of its precursor ornithine. Consistent with the hapX expression pattern, HapX-deficiency was deleterious with respect to growth rate and conidiation during iron depleted but not iron-replete conditions. HapX-deficiency caused significant attenuation of virulence in a murine model aspergillosis underlining that A. fumigatus faces iron starvation in the host and that the HapX-dependent metabolic reprogramming is therefore crucial for virulence.
2010-07-01 | GSE22052 | GEO
Project description:Trade-offs often occurs during experimental evolution. For example, the degeneration of growth in glucose was found in a galactose adapted yeast. Here, we isolated one Lactococcus lactis mutant using experimental on maltose. The mutant grows normally on glucose, but faster than the wild-type on maltose and galactose. DNA microarray analysis and whole genome re-sequencing were applied to disclose the crucial points that determine the phenotype.
2016-12-31 | GSE56042 | GEO
Project description:Comparative transcriptome analysis of E. faecium E1162 and its isogenic mdxR deletion mutant during growth in M1 with maltose in mid-exponential phase (A660 = 0.3)
2013-10-09 | E-MEXP-3759 | biostudies-arrayexpress
Project description:Prolonged cultivation (>25 generations) of Saccharomyces cerevisiae in aerobic, maltose-limited chemostat cultures led to profound physiological changes. Maltose hypersensitivity was observed when cells from prolonged cultivations were suddenly exposed to excess maltose. This substrate hypersensitivity was evident from massive cell lysis and loss of viability. During prolonged cultivation at a fixed specific growth rate, the affinity for the growth-limiting nutrient (i.e., maltose) increased, as evident from a decreasing residual maltose concentration. Furthermore, the capacity of maltose-dependent proton uptake increased up to 2.5-fold during prolonged cultivation. Genome-wide transcriptome analysis showed that the increased maltose transport capacity was not primarily due to increased transcript levels of maltose-permease genes upon prolonged cultivation. We propose that selection for improved substrate affinity (ratio of maximum substrate consumption rate and substrate saturation constant) in maltose-limited cultures leads to selection for cells with an increased capacity for maltose uptake. At the same time, the accumulative nature of maltose-proton symport in S. cerevisiae leads to unrestricted uptake when maltose-adapted cells are exposed to a substrate excess. These changes were retained after isolation of individual cell lines from the chemostat cultures and nonselective cultivation, indicating that mutations were involved. The observed trade-off between substrate affinity and substrate tolerance may be relevant for metabolic engineering and strain selection for utilization of substrates that are taken up by proton symport. Keywords: Evolution
2007-08-31 | GSE8897 | GEO
Project description:To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iron excess and is thereby crucial for virulence. Previous studies indicated that a HapX homodimer interacts with the CCAAT-binding complex (CBC) to cooperatively bind bipartite DNA motifs; however, the significance of the HapX and CBC interaction and the mode of HapX-DNA recognition had not been resolved. In this study, we characterized the genome-wide binding profiles of HapX using the chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Our ChIP-seq results, in combination with in vitro surface plasmon resonance analysis, phylogenetic comparison, and genetic analysis, revealed an astonishing plasticity of the CBC:HapX DNA-recognition mode.
2019-12-31 | GSE129969 | GEO
Project description:Transcriptional analysis of the effects of sugar source in S. mutans RNA was extracted from 4 replicate samples of S. mutans UA159, UA159 grown in glucose or maltose in continuous culture to steady-state pH values of 7 or 5. RNA was labeled with Cy3. For each replicate, labeled RNA was hybridized to slides along with Cy5-labeled reference RNA, extracted from S. mutans UA159 cultures grown to mid-log.
2014-06-01 | E-GEOD-55952 | biostudies-arrayexpress
Project description:The airborne fungus Aspergillus fumigatus causes opportunistic infections in humans with high mortality rates in immunocompromised patients. Previous work established that the bZIP transcription factor HapX is essential for virulence via adaptation to iron limitation by repressing iron-consuming pathways and activating iron acquisition mechanisms, such as the high-affinity siderophore-assisted iron uptake system. Moreover, HapX was shown to be essential for transcriptional activation of vacuolar iron storage and iron-dependent pathways in response to iron availability. Here, we demonstrate that HapX has a very short half-life during iron starvation, which is further decreased in response to iron, while siderophore biosynthetic enzymes are very stable. Immunoprecipitation experiments followed by LC-MS/MS analysis identified Fbx22 and SumO as HapX interactors and, in agreement, HapX post-translational modifications including ubiquitination of lysine161, sumoylation of lysine242 and phosphorylation of threonine319. All three modifications were enriched in the immediate adaptation from iron-limiting to iron-replete conditions. Interfering with these post-translational modifications, either by point mutations or by inactivation, of Fbx22 or SumO, altered HapX degradation, heme biosynthesis and iron resistance to different extents. Consistent with the need to regulate HapX protein levels, overexpression of hapX caused significant growth defects under iron sufficiency. Taken together, our results indicate that post-translational regulation of HapX is important to control iron homeostasis in A. fumigatus.
2021-07-20 | PXD026889 | Pride
Project description:Growth to mid exponential phase in M9 minimal media supplemented with 0.5% maltose versus growth in rich LB media Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Media: M9 minimal media with 0.5% maltose Keywords: Logical Set
2006-05-20 | GSE4876 | GEO
Project description:Commensal (symbiont) bacteria form communities in various regions of the bodies of vertebrates. Phylogenetic analysis of gut communities is advanced, but the relationships, especially at the trophic level, between commensals that share gut habitats of monogastric animals have not been investigated to any extent. Lactobacillus reuteri strain 100-23 and Lactobacillus johnsonii strain 100-33 cohabit in the forestomach of mice. According to the niche exclusion principle, this should not be possible because both strains utilise the two main fermentable carbohydrates present in the stomach digesta: glucose and maltose. We show, based on gene transcription analysis, in vitro physiological assays, and in vivo experiments that the two strains can co-exist in the forestomach habitat because L. reuteri 100-23 transports maltose into its cells more efficiently than does L. johnsonii 100-33. Conversely, strain 100-33 transports glucose more efficiently than 100-23. As a result, 100-23 shows a preference for growth using maltose, whereas 100-33 prefers glucose. Mutation of the maltose phosphorylase gene (malA) of strain 100-23 prevented its growth on maltose-containing culture medium, and resulted in the numerical dominance of 100-33 in the forestomach. The fundamental niche of L. reuteri 100-23 in the mouse forestomach can be defined in terms of glucose and maltose fermentation. Its realised niche when L. johnsonii 100-33 is present is maltose fermentation. Hence nutritional adaptations provided niche differentiation that enabled cohabitation by the two strains through resource partitioning in the mouse forestomach. This real life, trophic phenomenon conforms to a mathematical model.
2010-12-11 | GSE24472 | GEO