Régulation des facteurs de la virulence bactérienne: plasticité du génome et dynamique de la machinerie de transcription – Régupath

Fundamental biological processes are controlled by the coordination of genetic expression. Modification of this coordination may lead to severe dysfunction. Pathogenic bacteria coordinate very strictly expression of the genes required to infect and invade their host. Thus, understanding of the basic mechanisms allowing the coordination of the bacterial genetic program is of fundamental interest and a prerequisite for development of new methods to fight against pathogenic bacteria. The hypothesis driving this proposal is that the bacterial genetic response to a new environment depends on the dynamics of structural cooperation between the composition of transcriptional machinery (RNA polymerase and regulators) and the topology of gene promoters. The main goal of this project is to elucidate how the phytopathogenic enterobacterium Erwinia chrysanthemi integrates these two global levels of regulation of gene expression to adapt the transcription of its virulence genes in response to changes in environmental conditions, particularly those encountered during infection of its host plants. A multidisciplinary approach will be used, combining classical methods of microbiology, bacterial genetics, biochemistry, phytopathology and also global analysis of genome expression and mathematical modelling. This type of approach, hitherto inaccessible, has become feasible in bacteria due to the development of novel tools for genome-wide analyses of the coding and non-coding genome regions, and also, to an accumulated knowledge on gene expression and mathematical modelling of biological systems. This project is the result of the unique combination of the expertise of several groups studying different aspects of bacterial gene expression. This national consortium works in collaboration with several foreign groups that work on genetic regulation in other pathogenic enterobacteria such as E. carotovora and Salmonella typhimurium (Prof. GPC Salmond, University of Cambridge, UK; Dr Toth, SCRI Dundee, UK; Prof. Dorman, TCD Dublin, Ireland) or that possess a strong expertise in the integration of multifactorial control of bacterial gene expression (Prof. Muskhelishvili, International University of Bremen, Germany). The goal of this work is to obtain precise information about the mechanisms that allow bacteria to adapt their physiology to environmental challenges in order to facilitate the design of new antibacterial compounds. Experience of participants and high level international collaborations are a guarantee for providing high quality data and achievement of innovative results.