Abstract
Bacterial infections, especially those caused by biofilms, pose a serious threat to public health. In this work, we propose a glycopeptide-based antibiotic nano-adjuvant (GalAc-2) that can synergistically enhance the antibacterial activity of antibiotics through its biofilm inhibition activity. Our glycopeptide nanoparticles can be specifically activated by bacterial infection overexpressed lipase and sequentially enlarged by glycosyl exposure on the surface. The stability and bonding affinity of the nanoparticles were enhanced through the increase in β-sheet conformation. The bacterial growth inhibition rate of the mixture of levofloxacin (LEV) and GalAc-2 at 0.54 µg/mL was over sevenfold higher than that of LEV alone because of the electrostatic and multivalence LecA interactions that inhibited biofilm formation on the bacterial surface. Finally, the mixture of the antibiotic with GalAc-2 significantly inhibited the abscess exposed to skin infection and significantly reduced the infiltration of immune cells. We believe that GalAc-2 can be further used to enhance broad-spectrum antibiotic sensitization and prolong the lifetime of antibiotics.
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Acknowledgements
This work was supported by the National Key R&D Program of China (2018YFE0205400) and the National Natural Science Foundation of China (51873045). Dr. L.L. Li thanks the Youth Innovation Promotion Association, CAS (2017053).
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Lipase-activated glycopeptide nano-assemblies as an antibiotic nano-adjuvant to inhibit Pseudomonas aeruginosa biofilm and enhance antibacterial activity
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Song, Y., Zhang, J., Fei, Y. et al. Lipase-activated glycopeptide nano-assemblies as an antibiotic nano-adjuvant to inhibit Pseudomonas aeruginosa biofilm and enhance antibacterial activity. Sci. China Chem. 65, 2538–2547 (2022). https://doi.org/10.1007/s11426-022-1348-9
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DOI: https://doi.org/10.1007/s11426-022-1348-9