Descrizione del progetto
Nanosonde a base di glicani per rilasciare gli antibiotici nei batteri
I carboidrati presenti nella membrana cellulare svolgono ruoli di primaria importanza nell’adesione batterica. Queste interazioni sono caratterizzate da un’elevata specificità e deboli affinità verso i loro ligandi di carboidrati, che sono compensate da una presentazione di tali ligandi da parte dell’ospite in modo multivalente, oppure come aggregazioni sulla cellula o sulla superficie della mucosa. I disaccaridi possono fungere da vettori su nanoparticelle fluorescenti bifunzionalizzate per contribuire al rilascio intracellulare di altre porzioni di glicani non internalizzabili, impedendo il percorso di degradazione endosomiale e lisosomiale. Nanomateriali a base di carbonio fluorescenti, non tossici e solubili in acqua recentemente sviluppati hanno mostrato di essere in grado di etichettare sia i batteri gram-negativi che quelli gram-positivi. Il progetto BioNanoProbes, finanziato dall’UE, intende sviluppare una nuova classe di nanosonde a base di glicani per l’etichettatura e il rilascio degli antibiotici nei batteri.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
- natural sciencesphysical sciencesopticsmicroscopyconfocal microscopy
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
BS8 1QU Bristol
Regno Unito