Mouse spleen expression profile after systemic Candida glabrata infection
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ABSTRACT:
PROVIDER: PRJNA553465 | ENA |
REPOSITORIES: ENA
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Project description:Pleiotropic type I interferons (IFNs-I) fulfil multiple protective functions during infectious diseases, but can also exert detrimental effects for the host leading to immunopathology. Here, we report that IFNs-I promote the dysregulation of Fe homeostasis in macrophage populations and in the spleen during systemic infections with the intracellular pathogen Candida glabrata, leading to fungal survival and persistence. By using microarray expression profiling with RNA isolated from mouse spleens upon systemic Candida glabrata infection and subsequent in vitro interaction experiments we show that IFN-I signaling induces global transcriptional downregulation of key players in Fe homeostasis and profoundly alters Fe transport mechanisms within macrophages.
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2018-12-26 | GSE114175 | GEO
Project description:Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Derg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum.
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Project description:Total RNA versus genomic DNA hybridization on custom arrays designed for all Candida glabrata genes
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Project description:Our purpose is to clarify the global transcriptional profile in Candida glabrata phagocytized in human neutrophil.
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Project description:Total RNA versus genomic DNA hybridization on custom arrays designed for all Candida glabrata genes Total RNA was collected in mid-log phase from Candida glabrata cells grown in rich medium (abbreviated CM, in house recipe). RNA was then converted to cDNA, Cy3-labeled and hybridized competitively against Cy5 labeled genomic DNA from Candida glabrata
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Project description:Candida glabrata is an important human fungal pathogen leading cause of non-albicans Candida infections. C. glabrata exhibits resistance to key antifungal drugs, rapidly replicates and divides in host macrophages and withstands highly stressful host conditions. This study explores the molecular mechanisms underlying stress adaptations in C. glabrata that contribute to its pathogenicity. Our findings revealed that C. glabrata survives oxidative stress and amino acid starvation more effectively than S. cerevisiae, C. albicans, and C. auris. We noted that Gcn2 kinase and Gcn4 play critical roles in this adaptation as Gcn2 phosphorylates eIF2α and downregulates the global protein translation, activating GCN4. RNA sequencing of WT and gcn4 mutant revealed that GCN4 activation during stress orchestrates the expression of stress-responsive genes vital for survival during amino acid starvation and oxidative stress. Ultimately assisting in the stress adaptative transcriptome. Thus, this study highlights the critical role of the Gcn2–Gcn4 pathway in stress adaptation in C. glabrata.
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Project description:The transcription profile of Candida glabrata grown under two different Niacin limitation conditions were determined. Condition 1 is comparing log phase C. glabrata cells (O.D. 0.5-0.6) grown in synthetic medium containing 0.016 uM versus 3.25 uM nicotinic acid (NA), a common form of Niacin. The NA concentration of 3.25 uM is the standard concentration in synthetic complete (SC) medium. Condition 2 is comparing log phase C. glabrata cells (O.D. 0.4-0.6) grown in 3 individual human urine samples (supplemented with 2% glucose) versus in SC medium. Keywords: transcriptional profiling by microarray
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