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Vers une meilleure compréhension de la tolérance aux antibiotiques de biofilms bactériens cliniques

Abstract : Bacteria are microorganisms capable of growing independently in liquid media. However, as soon as they encounter a surface, either biotic or abiotic, bacteria favour a "community living" to protect themselves from external aggressions and survive in hostile environments. These bacterial communities, named biofilms, are present in all natural environments, including humans where they can cause severe infections when hosting pathogenic germs. It is now accepted that such biological edifices persist under antibiotics action. In addition to antibiotic 'resistance', which is associated with genetic mutations of bacteria, 'tolerance' is related with the specific structure and physiology of bacteria organized in biofilms. In this context, we took benefit from innovative high-resolution imaging techniques to better understand the mechanisms underlying antibiotics (vancomycin, daptomycin, rifampicin) (in)efficacy within S. aureus biofilms. In addition, we developed a model for prosthetic vascular graft infections in mice that allowed the visualization by fluorescence imaging of biofilms formed in vivo and subjected to the action of antibiotics. Considering the very limited antibiotics efficacy observed, we then focused on a better understanding of S. aureus bacterial biofilms tolerance towards antibiotics. To this purpose, our work was focused on the role of both the extracellular matrix and the physiology of bacteria included in biofilms. The crucial role of membrane fluidity was then demonstrated. This work allowed us to identify paths for the improvement of antibiotic therapy and to develop alternatives to this type of treatment.
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Submitted on : Thursday, November 1, 2018 - 1:01:12 AM
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Rym Boudjemaa. Vers une meilleure compréhension de la tolérance aux antibiotiques de biofilms bactériens cliniques. Biophysique [physics.bio-ph]. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS241⟩. ⟨tel-01910465⟩

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