Tuning of glyconanomaterial shape and size for selective bacterial cell agglutination

Multivalent glycosystems are potential candidates for anti-adhesive therapy, a non-lethal approach against the ever increasing antibiotic resistance of pathogenic bacteria. In order to fine-tune the glyconanomaterial size and shape for selective bacterial cell agglutination, herein we report the synthesis of sugar-coated dynamic and polymeric 3D-micelles and 1D-carbon nanotubes. The reported shot-gun like synthetic approach is based on the ability of diacetylenic-based neoglycolipids to self-assemble into micelles in water and hierarchically self-assemble into hemimicelles on a single-walled carbon nanotube surface. The affinity of the nanosystems was preliminarily assessed by enzyme-linked lectin assay (ELLA) using the mannose-specific Concanavalin A lectin as a model receptor. Relative binding potency enhancements, compared to methyl ¿-d-mannopyranoside used as control, from 10- to 25- to 2340-folds in sugar molar basis were observed when passing from 3D dynamic micelles to static micelles, to 1D-mannose coated carbon nanotubes, respectively, indicative of a significant cluster glycoside effect. Importantly, these results were confirmed in vivo showing that the 1D-glyconanoring-coated carbon nanotubes efficiently and selectively regulate the agglutination and proliferation of the enterobacteria Escherichia coli type 1 fimbriae. These findings highlight the potential of sugar coated nano-materials as novel and effective tools in the control of bacterial pathogenesis.Financial support was provided by the Andalusian Ministry of Economy, Science and Innovation (P07-FQM-2774 to NK, P11-FQM-8046 to IF, FQM-1467 to JMGF, P08-CTS-04297, and P11-CTS-7962 to REW), the PAIDI Program from the Andalusian Government (FQM-313 to NK, FQM-102 to IF, BIO-026 to REW), the Spanish Ministry of Economy and Competitiveness (CTQ2013-49066-C2-1-R to NK and SAF2013-44021R to EMSF) and the European Union Seventh Framework Programme (FP7-People2012-CIG, grant agreement no. 333594 to EMSF). The European Regional Development Fund (FEDER) and the European Social Fund (ESF) are also acknowledged. MA was a recipient of a MAECAECID PhD fellowship. JJC was a recipient of a JAE-CSIC postdoctoral fellowship. EFG is a recipient of a fellowship from Junta de Andalucia.Peer Reviewe