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Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis

ABSTRACT: Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis

PROVIDER: PRJNA508086 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8272494.fastq.gz	Fastqsanger.gz
	SRR8272495.fastq.gz	Fastqsanger.gz
	SRR8272496.fastq.gz	Fastqsanger.gz
	SRR8272497.fastq.gz	Fastqsanger.gz

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Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis

Project description:Candida albicans, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron-limitation using Deferasirox (an FDA approved iron chelator for treatment of patients with iron overload) during murine OPC; and assessed Deferasirox-treated C. albicans for its interaction with human oral epithelial (OE), neutrophils, and antimicrobial peptides. Therapeutic Deferasirox treatment significantly reduced salivary iron levels while a non-significant reduction in fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model, resulted in significant reduction of C. albicans colony forming units (CFU)/g of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans harvested from tongues of animals undergoing preventive treatment had differential expression of 106 genes, including those involved in iron metabolism, adhesion, and response to host innate immunity. Moreover, Deferasirox-treated C. albicans cells had two-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress); and reduced adhesion and invasion of OE cells, in vitro. Thus Deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence

2018-12-04 | GSE123277 | GEO

Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis.

Project description:Candida albicans, the causative agent of mucosal infections, including oropharyngeal candidiasis (OPC), as well as bloodstream infections, is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off-label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence, while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron limitation using deferasirox (an FDA-approved iron chelator for the treatment of patients with iron overload) during murine OPC and assessed deferasirox-treated C. albicans for its interaction with human oral epithelial (OE) cells, neutrophils, and antimicrobial peptides. Therapeutic deferasirox treatment significantly reduced salivary iron levels, while a nonsignificant reduction in the fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model resulted in a significant reduction in the number of C. albicans CFU per gram of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans cells harvested from the tongues of animals undergoing preventive treatment had the differential expression of 106 genes, including those involved in iron metabolism, adhesion, and the response to host innate immunity. Moreover, deferasirox-treated C. albicans cells had a 2-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress) and reduced adhesion to and invasion of OE cells in vitro Thus, deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence.

| S-EPMC6437492 | biostudies-literature

Tongue RNA expression after oropharyngeal candidiasis in mice deficient in CCL28

Project description:We report the RNA expression using RNAseq in tongue tissue of mice with and without infection with oropharyngeal candidiasis. CCL28 KO mice are compared to C57BL/6 WT mice.

2024-01-25 | GSE165545 | GEO

Deferasirox, an iron chelator, impacts myeloid differentiation by modulating NF-kB activity via mitochondrial ROS

Project description:Deferasirox (DFX) can improve erythropoiesis in patients with MDS. We sought to test how these changes occur and whether myelopoiesis broadly is affected by analyzing neutrophils and neutrophil precursors treated with DFX.

2024-09-27 | GSE274956 | GEO

Deferasirox, an iron chelator, impacts myeloid differentiation by modulating NF-kB activity via mitochondrial ROS

Project description:Deferasirox, an iron chelator, impacts myeloid differentiation by modulating NF-kB activity via mitochondrial ROS

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Gene expression profiling in myelodysplastic syndrome patients treated with deferasirox

Project description:Deferasirox (DFX) is an oral iron chelator used to reduce iron overload caused by frequent red blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study molecular mechanisms by which DFX improves outcome in MDS, we analyzed gene expression patterns in MDS patients before and after DFX therapy.

2020-11-04 | GSE160727 | GEO

Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients

Project description:The iron chelator deferasirox is widely used in patients with iron overload. Patients with low-grade myelodysplastic syndromes (MDS) get transfusion dependency and need to be treated with deferasirox to avoid iron overload. Moreover, in some patients an increase in both erythroid and platelets have been observed after deferasirox therapy. However, the mechanisms involved in these clinical findings are poorly understood. The aim of this work was to analyze, in patients treated with deferasirox, the changes in the gene expression profile after receiving the treatment. A total of fifteen patients with the diagnosis of low-grade MDS were studied. Microarrays were carried out in RNA from peripheral blood before and after 14 weeks of deferasirox therapy. Changes in 1,457 genes and 54 miRNAs were observed: deferasirox induced the downregulation of genes related to the Nf kB pathway leading of an overall inactivation of this pathway. In addition, the iron chelator also downregulated gamma interferon. Altogether these changes could be related to the improvement of erythroid response observed in these patients after therapy. Moreover, the inhibition of NFE2L2/ NRF2, which was predicted in silico, could be playing a critical role in the reduction of reactive oxygen species (ROS). Of note, miR-125b, overexpressed after deferasirox treatment, could be involved in the reduced inflammation and increased hematopoiesis observed in the patients after treatment. In summary this study shows, for the first time, the mechanisms that could be governing deferasirox impact in vivo.

2019-12-13 | GSE141958 | GEO

RNA-seq of Highly Metastatic and Lowly Metastatic 4T1 Single Clones Treated with Iron Chelator Deferasirox (DFX)

Project description:RNA-seq of Highly Metastatic and Lowly Metastatic 4T1 Single Clones Treated with Iron Chelator Deferasirox (DFX)

| PRJNA902387 | ENA

RNA-seq of Highly Metastatic and Lowly Metastatic 4T1 Single Clones Treated with Iron Chelator Deferasirox (DFX)

Project description:Using bulk RNA-seq, the transcriptional profile of two cell lines with high or low metastatic properties derived from single clones of the murine 4T1 cell line treated or untreated with iron chelator DFX was analyzed in order to determine the mechanism underlying the inhibition preference of DFX for highly metastatic 4T1 cells.

2022-11-16 | GSE218133 | GEO

Tongue RNA expression after oropharyngeal candidiasis in mice deficient in CCL28

Project description:Tongue RNA expression after oropharyngeal candidiasis in mice deficient in CCL28

| PRJNA694936 | ENA