Unknown,Transcriptomics,Genomics,Proteomics

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Enterococcus faecalis EfaR mutant transcriptome profile

ABSTRACT: Metal ions are important cofactors of inumerous enzymes and can interfere in many biological processes. Manganese is a particularly relevant metal as it is also involved in protection from oxidative stress and several Mn-dependent regulators have been shown to have a role in bacterial pathogenicity. A putative DNA-binding motif, here called efa motif was discovered in the promoter regions of genes previously shown to be differentially expressed in the presence of excess zinc, manganese and copper ions. This motif led to the finding and study of the genes putatively involved in the maintenance of manganese homeostasis in E. faecalis. In these genes is included the efaCBA operon, regulated by the Mn-dependent regulator EfaR. Other genes with this efa motif are shown to be regulated by EfaR. Regulation of these efa motif genes by EfaR is discussed as well as some clues on metal interaction with EfaR. Experiments mimicking conditions occurring on biological processes in the host showed that an EfaR plays an important role in biological processes crucial for E. faecalis colonization and virulence. Comparison of the transcriptome profiles of Enterococcus faecalis strains VE14089 and VE14089 efaR::tet 2 condition experiment: E. faecalis VE14089 cells vs. E. faecalis VE14089 efaR::tet cells

ORGANISM(S): Enterococcus faecalis

SUBMITTER: Marta Abrantes

PROVIDER: E-GEOD-33698 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:We assessed changes in gene expression in response to manganese availability for the human pathogen Corynebacterium diphtheriae. Total RNA was harvested from wild-type C. diphtheriae strain 1737 and an isogenic ΔmntR (dip0619) grown in semi-defined metal-limited media (mPGT) without or with 5 µM manganese chloride supplementation. Three biological replicates were prepared and five genes were assessed by real-time PCR to validate the array results: dip0124, dip0169, dip0615, dip1923, and dip2261. (Abstract) Corynebacterium diphtheriae is the causative agent of a severe respiratory disease in humans. The bacterial systems required for infection are poorly understood, but the acquisition of metals such as manganese (Mn) are likely critical for host colonization. MntR is a Mn-dependent transcriptional regulator in C. diphtheriae and was previously shown to repress the expression of the mntABCD genes, which encode an ABC metal transporter. However, other targets of Mn and MntR regulation in C. diphtheriae have not been identified. In this study, we use comparisons between the gene expression profiles of wild-type C. diphtheriae strain 1737 grown without or with Mn supplementation and comparisons of gene expression between wild-type and an mntR mutant to characterize the C. diphtheriae Mn and MntR regulon. MntR was observed to both repress and induce the expression of various target genes in a Mn-dependent manner. Genes induced by MntR include the Mn-superoxide dismutase, sodA, and the putative ABC transporter locus, iutABCD. DNA binding studies showed that MntR interacts at the promoter regions for several genes identified in the expression study, and a 17-bp consensus MntR DNA binding site was identified. We found that an mntR mutant displayed increased sensitivity to Mn and Cd that could be alleviated by the additional deletion of the mntA-D transport locus, providing evidence that the MntABCD transporter functions as a Mn uptake system in C. diphtheriae. The findings in this study further our understanding of metal uptake systems and global metal regulatory networks in this important human pathogen.

Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

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Enterococcus faecalis EfaR mutant transcriptome profile

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