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Banking on new antimicrobials: translational fidelity impairment (BONAFIDE)
Date du début: 1 mars 2012, Date de fin: 28 févr. 2014 PROJET  TERMINÉ 

"Infectious diseases represent an incessant threat for the human population worldwide. The rapid evolution and flexible metabolism of bacterial pathogens have caused a staggering global rise in antibiotic resistance. Our project aims to contribute to the pressing need for discovery of new antibacterial targets.The project will combine the applicant`s expertise in molecular biology and biochemistry, together with the competence of the host lab in infection biology, bioinformatics and high-through-put methods, to evaluate potential targets for new antimicrobials development.Protein biosynthesis accuracy is an integral part of the living cell health. Errors during translation of genetic information into proteins may lead to nonfunctional and toxic product formation. We propose to evaluate frameshifting, the most severe type of translational inaccuracy, in a systematic and quantitative fashion as means to defeat bacterial pathogens. Our preliminary data show that it is possible to invoke avirulence by targeting frameshifting control in the pathogen Salmonella.To reach our objective, we have developed a fluorescence-based tool to monitor translational mistakes in vitro and in vivo using flow cytometry. We will collaborate with core facilities to use proteomics and gene expression profiling to decipher downstream effects of mistranslation. The results will be validated in the murine model of typhoid fever. These data will be used to create an in silico model for Salmonella that, fed by genomic information of other bacterial pathogens, could predict potential broad-spectrum drug targets.The academic benefit of the project involves promotion of an interdisciplinary approach and mutual exchange of state-of-the-art methodology between the host lab and the researcher. The researcher will enhance her individual competences as an independent investigator, master cutting-edge techniques, and strengthen her tutor skills within proposed out-reach activities."