Abstract
Background
Bacterial resistance to antibiotics is one of the biggest challenges facing medicine today. Anti-adhesive therapy, using inhibitors of bacterial adhesion to epithelial cells, one of the first stages of infection, is a promising approximation in this area. The size, shape, number of sugar and their placement are variables that have to be taken into account in order to develop multivalent systems able to inhibit the bacterial adhesion based on sugar-lectin interaction.
Materials and methods
In the present work we report a modular approach for the synthesis of water-soluble 1D-carbon nanotube-sugar nanoconstructs, with the necessary flexibility to allow an efficient sugar-lectin interaction. The method is based on the reaction of aryl diazonium salts generated in situ from aniline-substituted mannose and lactose derivatives with single wall carbon nanotubes (SWCNTs) sidewalls.
Results
Two hybrid nanosystems, I-II, exposing mannose or lactose and having a tetraethylene glycol spacer between the sugar and the nanotube sidewall were rapidly assembled and adequately characterized. The sweet nano-objects were then tested for their ability to agglutinate and selectively inhibit the growth of uropathogenic Escherichia coli. These studies have shown that nanosystem I, exposing mannose on the nanotube surface is able to agglutinate and to inhibit the bacterial growth unlike nano-objects II exposing lactose.
Conclusion
The results reported constitute a proof of principle in using mannose-coated 1D-carbon nanotubes as antiadhesive drugs that compete for FimH binding and prevent the uropathogenic bacteria from adhering to the urothelial surface.
Acknowledgments
Financial support was provided by the PAIDI Program of the Andalusian Government (FQM-313 to NK, BIO-026 to REW), and the Spanish Ministry of Economy and Competitiveness (CTQ2016-78580-C2-1-R to NK) the University of Seville (V PLAN PROPIO to REW). The European Regional Development Fund (FEDER) and the European Social Fund (ESF) are also acknowledged. We thank the Center of Research Technology and Innovation of the University of Seville (CITIUS) for the use of TEM, AFM, and NMR facilities. Mohyeddin Assali current adress: Department of Pharmacy, Faculty of Medicine and Health Science, An Najah National University.
Disclosure
ERB is recipient of an FPU PhD fellowship from the Spanish Ministry of Education, Culture and Sport. EF is recipient of a fellowship from the Junta de Andalucia (P11-CTS-7962/FEDER). The authors report no other conflicts of interest in this work.