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Dynamique réactionnelle d'antibiotiques au sein des biofilms de Staphylococcus aureus : apport de la microscopie de fluorescence multimodale

Abstract : Bacteria form architecturally complex communities adherent to surfaces, known as biofilms. These structured living cells are ubiquitous and found in natural, industrial and medical environments. They can affect our health when they host pathogens as the well known Staphylococcus aureus species which constitute the main purpose of this thesis. This bacteria is one of the major causes of chronic and nosocomial infections, most often involving biofilms. It is now recognized that such biostructure is a true shield against the action of antimicrobial agents and the host immune system. In addition to the genetic resistance of pathogenic bacteria to antibiotics, the chemical and biological heterogeneity of biofilms could be the cause of these phenomena of tolerance and apparition of chronic infections. This work aimed at studying of the action of vancomycin on S. aureus biofilms. While the knowledge on the reactivity of this key antibiotic with S. aureus bacteria comes mainly from studies of planktonic cells, the originality of our approach was to study the diffusion-reaction processes of vancomycin in situ in the thickness of biofilms using particularly advanced fluorescence imaging tools (Time-Lapse, FLIM, FRAP and FCS). We thus assess its bioavailability in the exopolymeric matrix, and the impact of the cell physiology of bacteria included in biofilms on the activity of this antibiotic when used alone or in combination with rifampicin. This multidisciplinary approach has allowed a better understanding of the mechanisms involved in the particular tolerance of these biostructures to the action of antibiotics, and underlines the emergency to develop preventive approaches such as early diagnosis of infections involving biofilms.
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Samia Daddi Oubekka. Dynamique réactionnelle d'antibiotiques au sein des biofilms de Staphylococcus aureus : apport de la microscopie de fluorescence multimodale. Sciences agricoles. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA112011⟩. ⟨tel-00713410⟩

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