Affiliation:
1. State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering Southeast University 2 Sipailou Nanjing 210096 P. R. China
Abstract
AbstractStaphylococcus aureus (S. aureus) remains a leading cause of bacterial infections. However, eradication of S. aureus infections with common antibiotics is increasingly difficult due to outbreaks of drug resistance. Therefore, new antibiotic classes and antibacterial strategies are urgently in demand. Herein, it is shown that an adamantane‐peptide conjugate, upon dephosphorylation by alkaline phosphatase (ALP) constitutively expressed on S. aureus, generates fibrous assemblies in situ to combat S. aureus infection. By attaching adamantane to a phosphorylated tetrapeptide Nap‐Phe‐Phe‐Lys‐Tyr(H2PO3)‐OH, the rationally designed adamantane‐peptide conjugate Nap‐Phe‐Phe‐Lys(Ada)‐Tyr(H2PO3)‐OH (Nap‐FYp‐Ada) is obtained. Upon bacterial ALP activation, Nap‐FYp‐Ada is dephosphorylated and self‐assembles into nanofibers on the surface of S. aureus. As revealed by cell assays, the assemblies of adamantane‐peptide conjugates interact with cell lipid membrane and thereby disrupt membrane integrity to kill S. aureus. Animal experiments further demonstrate the excellent potential of Nap‐FYp‐Ada in the treatment of S. aureus infection in vivo. This work provides an alternative approach to design antimicrobial agents.
Funder
National Natural Science Foundation of China
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
6 articles.
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