ERA | Epigenetic Regulation in Acinetobacter baumannii

Summary
Gene expression in bacteria is regulated by a multitude of mechanisms to facilitate adaptation to changing environmental conditions and during infection, which is key to their evolutionary success. To ensure that genes are only expressed in the right place and at the right time, access of transcription factors to promoters that drive gene expression can be controlled by DNA binding proteins and DNA methylation. DNA methylation is a seemingly simple, yet powerful mechanism mediated by methyltransferases (MTases) of restriction-modification (R-M) systems or orphan MTases which methylate specific genomic sites and can modulate transcription factor binding thereby regulating gene expression. Although epigenetic regulation is widespread in bacteria, the exact regulatory mechanisms are often unknown. Epigenetic regulation is often found in pathogenic bacteria and it was shown that methylation can affect their virulence, biofilm formation and other important features. In this project, we will use the WHO priority pathogen Acinetobacter baumannii as a model to decipher epigenetic regulation. A. baumannii strains encode from one to ten different MTases and it was shown that the deletion of the most conserved A. baumannii MTase decreased motility and virulence suggesting a gene regulatory role for this MTase. This project will investigate the impact of MTases on epigenetic gene regulation of A. baumannii using bioinformatics and functional genomic approaches to uncover their role for A. baumannii biology. Considering regulatory MTases as a potential drug target, understanding epigenetics would inform new approaches for the treatment of A. baumannii infections. Additionally, the distribution of R-M system genes in different strains of bacteria can be useful in phage therapy development to create the phage resistant to the R-M systems of the most dangerous strains.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/896441
Start date: 01-07-2020
End date: 30-06-2022
Total budget - Public funding: 196 590,72 Euro - 196 590,00 Euro
Cordis data

Original description

Gene expression in bacteria is regulated by a multitude of mechanisms to facilitate adaptation to changing environmental conditions and during infection, which is key to their evolutionary success. To ensure that genes are only expressed in the right place and at the right time, access of transcription factors to promoters that drive gene expression can be controlled by DNA binding proteins and DNA methylation. DNA methylation is a seemingly simple, yet powerful mechanism mediated by methyltransferases (MTases) of restriction-modification (R-M) systems or orphan MTases which methylate specific genomic sites and can modulate transcription factor binding thereby regulating gene expression. Although epigenetic regulation is widespread in bacteria, the exact regulatory mechanisms are often unknown. Epigenetic regulation is often found in pathogenic bacteria and it was shown that methylation can affect their virulence, biofilm formation and other important features. In this project, we will use the WHO priority pathogen Acinetobacter baumannii as a model to decipher epigenetic regulation. A. baumannii strains encode from one to ten different MTases and it was shown that the deletion of the most conserved A. baumannii MTase decreased motility and virulence suggesting a gene regulatory role for this MTase. This project will investigate the impact of MTases on epigenetic gene regulation of A. baumannii using bioinformatics and functional genomic approaches to uncover their role for A. baumannii biology. Considering regulatory MTases as a potential drug target, understanding epigenetics would inform new approaches for the treatment of A. baumannii infections. Additionally, the distribution of R-M system genes in different strains of bacteria can be useful in phage therapy development to create the phage resistant to the R-M systems of the most dangerous strains.

Status

CLOSED

Call topic

MSCA-IF-2019

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2019
MSCA-IF-2019