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Epigenetic Regulation in Acinetobacter baumannii

Project description

DNA methylation in bacteria: a new drug target?

During environmental adaptation and infection, bacteria change their gene expression through various mechanisms including DNA methylation. Methylation is a powerful process that modulates transcription factor binding at specific genomic sites and hence ensures that genes are expressed in the right place and at the right time. The EU-funded ERA project is investigating the epigenetic mechanisms encountered in the opportunistic pathogen Acinetobacter baumannii. The idea is to decipher how methylation can affect bacteria virulence, biology and behaviour. Scientists will focus on methyltransferases as a potential drug target hoping to develop new approaches for the treatment of Acinetobacter baumannii infections.

Objective

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.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Net EU contribution
€ 196 590,72
Address
COLLEGE GREEN TRINITY COLLEGE
D02 CX56 Dublin
Ireland
Region
Ireland Eastern and Midland Dublin
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 196 590,72