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Non-coding RNAs in bacterial pathogenicity

Final Report Summary - BACRNAS (Non-coding RNAs in bacterial pathogenicity)

The BACRNAS team studied the role of non-coding RNAs (ncRNAs) in the regulation of bacterial virulence with the long-term objective to generate fundamental knowledge that can be directly applicable for therapeutic interventions to combat bacterial infections. In bacteria, small ncRNAs are involved in the regulation of a growing number of adaptive processes, like quorum sensing, transition to stationary phase, iron homeostasis, the SOS response, and bacterial virulence. Antisense RNAs, a class of ncRNAs that act by base-pairing to RNA targets, are responsible for the maintenance of many bacterial plasmids carrying antibiotic resistance genes. In the project performed by this consortium, they studied ncRNAs in pathogenic bacteria like Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes and Listeria monocytogenes. While studying the functions of ncRNAs, they discovered new RNA regulatory networks that control bacterial pathogenesis and related mechanisms like bacterial stress and environmental adaptation.

Infectious diseases are the second-ranking cause of death worldwide. Yet, despite increasing incidence of bacterial resistance to existing drugs, antibiotics development and discovery in the pharmaceutical industry is declining. 'We need new approaches, beginning with the recognition that the antibiotic crisis of wealthy and poor countries are the same' (quote by Carl Nathan, 21 October 2004, Nature). Many of the drugs used to treat bacterial infections target just a few classes of enzymes, briefly those involved in synthesis of proteins, nucleic acids, cell wall or folate. The objective was to explore a completely new class of molecules as potential targets for bacterial treatment: regulatory ncRNA networks involved in the establishment of bacterial pathogenicity.

The strength of the consortium rose from the merging of several internationally recognised expertises / competences in complementary research fields including microbial pathogenesis, bacterial physiology, RNA biology, bioinformatics, biochemistry and biophysics. Starting out from a genome-wide search for novel ncRNAs, their involvement in bacterial pathogenicity is being investigated by a variety of tools. A multi-disciplinary approach filters the most promising targets in the regulatory RNA networks involved in bacterial pathogenicity for further exploitation as a route to novel therapeutic agents against bacterial infections. This consortium applied the specific experience of individual partners in the use of complementary and sophisticated approaches. The project significantly contributed to the conceptual and technological advancement of the state of the art, and has adapted topical biotechnological, bacterial and genomic research.

The consortium vividly transferred the new knowledge about the role of ncRNAs in bacterial pathogenicity in talks and posters to the scientific community at numerous international conferences. They were invited for various talks in seminars and lectures at national and international institutions and meetings. The plan was checked regularly for changes and adaptations but kept the same during the lifetime of the project. Although no patents could be submitted, many protocols, methods and new insights into the project topic were published in 56 papers in journals with a high impact factor during the lifetime of BACRNAs. Eight papers were jointly published. The consortium published a description of the project BACRNAs in the EC funded book 'Fundamental genomics book' in 2008. It also published 'Searching for novel targets to fight bacterial Infections' in the journal eStrategies in 2009. The consortium is also about to create a review about the role of ncRNAs in bacterial pathogenicity. Further press releases and publications, which are suitable for a broader public were not published since appropriate results were not available. However, the partners were involved in the organisation and co-organisation of frequent meetings, workshops and conferences. With the EMBO workshop on 'New function of regulatory RNAs in pro- and eucaryotes", they succeed to create and organise a very successful closure of BACRNAS and in the same time opening of a discussion platform for future projects.

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