Objective Combating bacteria with antibiotics is an endless race because bacteria acquire antibiotic resistance (AR) genes easily from unknown environmental sources. Until now, understanding and control of AR spread was attempted through the precise descriptions of AR genes presently found in hospitals, and inference from this of the working mechanisms of dispersion (epidemiological approach). We think that an appropriate long-term public health objective would be to elucidate the molecular mechanisms behind the observed AR spread in a concerted strategy targeting the dissemination modules, from AR recruitment to their ultimate acquisition by bacterial pathogens. Thus, the focus of this project is to explore a mechanistic approach to combat AR. A coherent picture, which could explain the road to multiple AR in gram-negative species, is beginning to emerge from research on gene mobility. Starting from the superintegrons, which could be considered as the "cradles" of many AR, integron cassettes are recruited into integron platforms carried by transposons or plasmids. Insertion sequences (IS) capture genes or integron platforms to form transposons, which are subsequently translocated to conjugative plasmids. Plasmids transfer AR and establish themselves with variable efficiency in pathogenic bacteria. Finally, plasmids need to be stably inherited once they established themselves in a recipient cell. Specific mechanisms ensure that plasmid-free cells are eliminated. The objectives of CRAB deal with each of the dissemination modules in this chain ' integrons (WP1), transposons (WP2), conjugative plasmids (WP3) and stability modules (WP4) ' in a concerted approach. We concentrate on the as yet improperly studied aspects of these mechanisms. WP1: mechanism of integron cassette recombination, signals triggering integrase expression and molecular evolution of gene cassettes. WP2: Propensities of three major classes of IS to acquire, stabilise and vehicle AR genes and identification... Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistancenatural sciencesbiological sciencesmolecular biologymolecular evolution Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2004-2.1.2-2 - The role of mobile genetic elements in the generation of antimicrobial resistance LSH-2004-2.1.2-3 - Improved understanding of ecological factors with impact on the genetic and molecular determinants of fitness and virulence of resistant bacterial pathogens Call for proposal FP6-2004-LIFESCIHEALTH-5 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator INSTITUT PASTEUR EU contribution No data Address 25- 28, rue du Docteur Roux PARIS France See on map Links Website Opens in new window Total cost No data Participants (7) Sort alphabetically Sort by EU Contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE France EU contribution No data Address Rue Michel Ange, 3 PARIS See on map Links Website Opens in new window Total cost No data UNIVERSIDAD DE CANTABRIA Spain EU contribution No data Address Vicerrectorado de Investigación, Pabellón de Gobierno, Avda de los Castros s/n SANTANDER See on map Links Website Opens in new window Total cost No data AGRICULTURAL BIOTECHNOLOGY CENTER Hungary EU contribution No data Address Szent-Györgyi Albert u. 4. pob 411 GÖDÖLLÖ See on map Links Website Opens in new window Total cost No data UNIVERSITAET GRAZ Austria EU contribution No data Address Universitaetsplatz 3 GRAZ See on map Links Website Opens in new window Total cost No data UNIVERSITÉ LIBRE DE BRUXELLES Belgium EU contribution No data Address 50 avenue F Roosevelt BRUXELLES See on map Links Website Opens in new window Total cost No data THE UNIVERSITY OF MANCHESTER United Kingdom EU contribution No data Address Oxford Road MANCHESTER See on map Links Website Opens in new window Total cost No data DELPHI GENETICS SA Belgium EU contribution No data Address Rue Adrienne Bolland 8 CHARLEROI See on map Links Website Opens in new window Total cost No data