Enzymatic Self-Assembly of Adamantane-Peptide Conjugate for Combating Staphylococcus aureus Infection.
basic_science · Level V
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- Record sourced from PubMed, PMID 36880480.
- Also identified by DOI 10.1002/adhm.202203283.
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Abstract
Staphylococcus 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(H<sub>2</sub> PO<sub>3</sub> )-OH, the rationally designed adamantane-peptide conjugate Nap-Phe-Phe-Lys(Ada)-Tyr(H<sub>2</sub> PO<sub>3</sub> )-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.
Medical subject headings
- Staphylococcal Infections
- Anti-Infective Agents