ERA · Epigenetic Regulation in Acinetobacter baumannii

Epigenetic Regulation in Acinetobacter baumannii

What is the problem/issue being addressed? Bacterial gene expression regulation allows bacteria to adapt to environmental changes. The primary and most well-studied mechanism of gene expression regulation is the interaction of specific proteins, called transcription factors, with DNA. DNA methylation can alter the affinity of transcription factors to their target sites, and, as a result, modulate gene expression. The impact of DNA methylation is global and affects different aspects of bacterial physiology. However, the functional mechanisms of the methylation effect on gene expression are unclear. DNA is methylated by specific proteins, called DNA methyltransferases. These proteins can be a part of bacterial Restriction-Modification (R-M) systems where they are used to differentiate methylated host DNA from unmethylated foreign DNA. In this project, ERA, the Fellow investigated the role of methylation in Acinetobacter baumannii. The understanding of regulatory networks in these bacteria is essential for the development of new drugs and the understanding of the mechanisms of antibiotic resistance. Why is it important for society? The project's results contribute to studying the bacterial pathogen ​ A. baumannii. In 2017, the World Health Organisation included these bacteria in the critical priority list of pathogens for new drug development. The results improved our knowledge of epigenetic regulation mechanisms in bacteria and the diversity of their defence systems. The obtained results can reveal potential new drug targets and achieve healthy lives for all people which is one of the UN Sustainable Development Goals. The project was carried out at the Microbiology Department of Trinity College Dublin, so some tasks were done as student projects. The solution to fundamental scientific problems is an essential part of student education. What are the overall objectives? The project included the following objectives, organised in Work Packages (WP). Objective 1 (WP1). Bioinformatic analysis of the diversity and distribution of R-M systems and orphan MTases in known ​ A. baumannii ​ genomes to reveal regulatory DNA methyltransferase. Objective 2 (WP2). Establishing the role of the most widespread MTases in global gene expression, fitness, and virulence in experimental fitness and antibiotic-resistance assays, and infection models. Objective 3 (WP3). Determination of the direct and indirect regulatory role of the MTases by experimental and bioinformatic methods. The project also includes WP4, Training, and WP5 - Data dissemination. In the project, the Fellow employed a powerful combination of whole-genomic and transcriptomic approaches and phenotypic assays to characterise the role of methylation in A. baumannii. The project revealed the effect of methylation on gene expression and pathogenic traits of the bacteria, including biofilm formation, and virulence.

Data: CORDIS, © European Union