Effect of Hst3p inhibition in Candida albicans: a genome-wide H3K56 acetylation analysis
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PROVIDER: PRJEB56012 | ENA |
REPOSITORIES: ENA
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Project description:Candida spp. represent the third most frequent worldwide cause of infection in Intensive Care Units (ICUs) with a mortality rate of almost 40%. The classes of antifungals currently available include azoles, polyenes, echinocandins, pyrimidine derivatives, and allylamines. However, the therapeutical options for the treatment of candidiasis are drastically reduced by the increasing antifungal resistance. The growing need of a more targeted antifungal therapy is limited by the concern of finding molecules that specifically recognize the microbial cell without damaging the host. Epigenetic writers and erasers have emerged as promising targets in different contexts, including the treatment of fungal infections. In C. albicans, Hst3p, a sirtuin that deacetylates histone H3K56ac, represents an attractive antifungal target as it is essential for the fungus viability and virulence. Although the relevance of such epigenetic regulator is documented for the development of new antifungal therapies, the molecular mechanism behind Hst3p-mediated epigenetic regulation remains unrevealed. Here, we provide the first genome-wide profiling of H3K56ac in C. albicans; H3K56ac enriched regions are associated with Candida sp. pathogenicity. Upon Hst3p inhibition, 447 regions gain H3K56ac. Importantly, these genomic areas contain genes encoding for adhesin proteins, degradative enzymes, and white-opaque switch. Moreover, our RNA-seq analysis revealed 1330 upregulated and 1081 downregulated transcripts upon Hst3p inhibition, and among them, 87 genes whose transcription upregulation correlates well with changes in promoter H3K56 acetylation, including some well-known regulators of phenotypic switching and virulence, confirming that Hst3p is an appealing target for the development of new potential antifungal target.
2023-02-04 | E-MTAB-12167 | biostudies-arrayexpress
Project description:In the present study, we investigated whether the acetylation of H3K56, known as relevant for C. albicans virulence, might affect the Candida-macrophages interaction. Therefore, by the mean of the non-specific Hst3 inhibitor nicotinamide (NAM), we evaluated whether the alteration of H3K56 acetylation would affect the secretion of soluble factors by C. albicans. In particular, we tested the effect of the two different Candida growth-conditioned media (with and without NAM) on murine macrophages at the morphological and functional levels. In addition, we analyzed transcriptome modifications and genome enrichment of H3K56ac in the same experimental conditions.
2024-07-29 | E-MTAB-13348 | biostudies-arrayexpress
Project description:Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homologue of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 -/- mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 -/- mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage.
2010-01-04 | GSE18936 | GEO
Project description:In the present study, we investigated whether the acetylation of H3K56, known as relevant for C. albicans virulence, might affect the Candida-macrophages interaction. Therefore, by the mean of the non-specific Hst3 inhibitor nicotinamide (NAM), we evaluated whether the alteration of H3K56 acetylation would affect the secretion of soluble factors by C. albicans. In particular, we tested the effect of the two different Candida growth-conditioned media (with and without NAM) on murine macrophages at the morphological and functional levels. In addition, we analyzed transcriptome modifications and genome enrichment of H3K56ac in the same experimental conditions.
2024-07-30 | E-MTAB-13387 | biostudies-arrayexpress
Project description:Genome-wide transcriptional profiles of Candida albicans without and with inhibition of an analog sensitive Ssn3 using 3-MB-PP1.
2021-06-01 | GSE171859 | GEO
Project description:Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homologue of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 -/- mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 -/- mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Four independent pairs of biological replicate samples were analyzed to compare RNA levels in wild-type and rtt109 -/- cells. Two experiments were performed: first, in unperturbed cells grown in YPD and second, in cells exposed to H2O2. To account for dye effects, two of the four samples for each experiment were analyzed using Cy3 labeling of the wild-type sample and Cy5 labeling of the mutant sample; the dyes were swapped for the other two biological replicates.
2010-05-16 | E-GEOD-18936 | biostudies-arrayexpress
Project description:Effect of doxorubicin on P-glycoprotein in Candida albicans
2017-01-24 | MSV000080501 | GNPS
Project description:Comparison of Candida albicans SC5314 treated with fludioxonil for 30 min and untreated controls under hyphae-inducing conditions
2012-10-01 | GSE39715 | GEO