Abstract
Bacterial infection and the increasing resistance of bacteria to commercially available antibiotics have long become a threat to global human health. Therefore, it is an urgent scientific issue to explore nonantibiotic antibacterials. In this paper, a mannose-decorated spermine derivative (PBI-spm-Man) was synthesized, which formed a self-assembled glycocluster with multivalent mannose moieties and concentrated cations. PBI-spm-Man as a nonantibiotic antibacterial agent showed potent antibacterial activity towards Escherichia coli (E. coli) through both mannose-FimH targeting and non-specific electrostatic interaction and functioned by damaging bacterial membrane. PBI-spm-Man also demonstrated antibacterial activity against representative Gram-positive bacteria Staphylococcus aureus (S. aureus) and intrinsically resistant bacteria Pseudomonas aeruginosa (P. aeruginosa). What is more exciting is that PBI-spm-Man could eliminate three clinical-isolated E. coli strains that are resistant to different antibiotics at around 20 μM. In vivo full-thickness wound healing results showed that the self-assembly of PBI-spm-Man not only reduced the residual bacteria at the wound site, but also promoted wound healing. This work represents a universal design strategy for nonantibiotic antibacterial agents based on multivalent glycoconjugates.
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