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Glycocluster inhibition effect on bacterial adhesion of Pseudomonas aeruginosa characterized by atomic force microscopy and spectroscopy : from molecule to cell

Francesca Zuttion 1
1 INL - C&N - INL - Chimie et Nanobiotechnologies
INL - Institut des Nanotechnologies de Lyon
Abstract : Pseudomonas aeruginosa (PA) is a human opportunistic pathogen responsible for 20% -30% of nosocomial infections in French hospitals. For healthy people, it presents no real danger, but for people with cystic fibrosis disease and immune-compromised patients, it is the leading cause of mortality and lung infections. PA has developed antibiotic multi-resistant strains and new and more effective therapeutic approaches are needed. It binds to the surface of the host cells by an interaction between proteins (lectins) present on the membrane and sugars of the host-cell membrane. The lectin-sugar interaction plays an important role in adherence of the bacteria and in the manufacture of a pathogenic biofilm.A new therapeutic approach is to create synthetic molecules (glycoclusters) of greater affinity than the natural sugars present on the cells. To this aim, more than 150 glycoclusters have been synthetized and screened to find the best candidate to inhibit the bacteria infection process. Some of them have been selected and studied by Atomic Force Microscopy (AFM). In particular, this thesis is devoted to study the lectin-glycocluster and cell-bacteria interactions by AFM. The combination of AFM imaging with molecular dynamic simulations let understanding the role of the geometry of the glycoclusters on the complex formation, while AFM spectroscopy accesses the lectin-glycocluster interaction forces at the molecular and cellular levels. The reduction of bacterial adhesion has been observed upon the addition of the glycocluster. This confirms the anti-adhesive properties of the glycocluster and validates the procedure. The ultimate goal is the identification of the best glycoclusters in order to develop new drugs.
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Francesca Zuttion. Glycocluster inhibition effect on bacterial adhesion of Pseudomonas aeruginosa characterized by atomic force microscopy and spectroscopy : from molecule to cell. Other. Université de Lyon, 2016. English. ⟨NNT : 2016LYSEC031⟩. ⟨tel-01657642⟩

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