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COMBATING RESISTANCE TO ANTIBIOTICS

Ziel

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...

Aufforderung zur Vorschlagseinreichung

FP6-2004-LIFESCIHEALTH-5
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