Description du projet
Des nanosondes à base de glycanes pour délivrer des antibiotiques aux bactéries
Les glucides de la surface cellulaire jouent un rôle clé dans l’adhésion des bactéries. Ces interactions présentent une spécificité élevée et de faibles affinités envers leurs ligands glucidiques, compensées par le fait que l’hôte présente les ligands glucidiques de manière multivalente ou sous forme d’amas à la surface des cellules ou des muqueuses. Un disaccharide peut servir de support à des nanoparticules fluorescentes bifonctionnalisées pour faciliter l’administration intracellulaire d’autres fragments de glycanes non internalisables, en évitant la voie de dégradation endosomale/lysosomale. Des nanomatériaux fluorescents hydrosolubles et non toxiques à base de carbone récemment mis au point ont démontré qu’ils pouvaient marquer les bactéries à Gram négatif et à Gram positif. Le projet BioNanoProbes, financé par l’UE, vise à développer une nouvelle classe de nanosondes à base de glycanes pour le marquage et l’administration d’antibiotiques aux bactéries.
Objectif
Methods for specific recognition and targeting of bacteria are of key importance in developing approaches to counter the growth of antimicrobial resistance (AMR). Cell surface carbohydrates play key roles in cell recognition mechanisms and bacterial adhesion. These key interactions typically exhibit high specificity and weak affinities toward their carbohydrate ligand. This low affinity is compensated in nature by the architecture of the protein, the host presenting the carbohydrate ligands in a multivalent manner or as clusters on the cell or mucosal surface. Glyco-nanomaterials offer the possibility of attaching several different molecules to the same nanoparticle while controlling the relative densities of these ligands. Recently, the Galan group demonstrated that a simple disaccharide, such as lactose can act as a “Trojan horse” on bi-functionalized fluorescent nanopartiples (CdSe QDs) to help intracellular delivery of other non-internalizable glycan moieties and largely avoid the endosomal/lysosomal degradative pathway. Following this, the group has developed a new class of water-soluble, non-toxic fluorescent carbon-based nanomaterials which are easily accessible from cheap carbohydrate starting materials and more excitingly, preliminary data have shown that these new carbon nanodots are able to label both Gram-negative and Gram-positive bacteria. Based on these exciting results, the aim of this project is to develop a new class of glycan-based nanoprobes for labelling and delivery of antibiotics into bacteria. The glycan-based nano pro-drugs will be evaluated in bacterial binding and killing assays and screened for selective labelling and drug release using confocal microscopy and TEM. This is a multidisciplinary project involving synthetic organic and materials chemistry, glycobiology and microbiology.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
- natural sciencesphysical sciencesopticsmicroscopyconfocal microscopy
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
BS8 1QU Bristol
Royaume-Uni