Télécharger le descriptif complet du sujet de thèse
Résumé du sujet :
The project involves a microbiology part (supervized by Houssein Benabdelhak, a microbiologist working at LIB) and a acoustic part (supervized by Nicolas Taulier). Thus, the project requires to handle microbiology approaches allowing to grow bacteria, to create mutants, or to extract transmembrane proteins from bacteria in order to insert them in liposomes. While the acoustic part will consist in studying the previous bacteria or liposomes containing bacterial proteins under an acoustic field, which acoustic parameters can be varied, in order to understand the mechanism of action of ultrasound.
Porins are membrane channel forming proteins which allow the selective diffusion of small hydrophilic molecules across the bacterial membrane. In this regard, most of antibiotics should pass through bacterial porins to reach their target. We have already shown that low-intensity ultrasound acts on the Escherichia coli OmpF and OmpC porins, lowering significantly the transmembrane transport of antibiotics. This is accomplished without inducing a membrane transient breakdown or a local temperature increase as sonoporation does. Thus, the interaction between porins and ultrasonic pressure wave is most probably of mechanical nature. The effect of low intensity ultrasound on transmembrane transport is poorly understood especially at the cell level. This fact is hindering the development of the above technology.
The goal of this project is to understand how to reduce the effectiveness of efflux pumps responsible for the expulsion of antibiotics making them multi-resistant to bacteria. We will first focus our investigation on E. Coli, which efflux pumps are composed of three subunit proteins: AcrA; AcrB and TolC. In vivo and in vitro measurements will be conducted to monitor the effect of changes in acoustic parameters on the effectiveness of antibiotics due to the reduction of efflux pump action.
Directeur de thèse :
- Nicolas TAULIER
Codirection éventuelle :
- Houssein Benabdelhak