Abstract:
A sustainable solution to the dramatic spread of antibiotic resistance threatening public health security is the development of antibiotic-free antimicrobial substances.Inspired by natural host defense mecha-nisms involving amino-terminal copper-nickel binding motif(ATCUN)antimicrobial peptides(AMPs),we have designed and prepared an artificial complex(Cu@G-AMPs)incorporating single-atom Cu cata-lysts for antibacterial therapy.The substrate of the complex,formed from guanine doped with abundant heteroatoms,anchored single Cu atoms with a coordination number of 2 and an average bond length of 1.91 A.Interestingly,Cu@G-AMPs,exhibiting Fenton-like catalytic activity,caused the inactivation of methicillin-resistant Staphylococcus aureus(MRSA)by generating and delivering reactive oxygen species(ROS)cargo.Mechanistically,the intrinsic stress response system of MRSA underwent an irreversible col-lapse when Cu@G-AMPs initiated its offensive program associated with non-specific targets.Furthermore,Cu@G-AMPs,which inherited the immunomodulatory properties of AMPs,sequentially car-ried out the functions of pulling edge closure,stabilizing granulation tissue,promoting collagen fiber pro-liferation,alleviating inflammation,and promoting neovascularization in wound areas infected by MRSA.Our results show that Cu@G-AMPs will provide a new perspective on untangling the complex regulatory networks that resistant bacteria have cultivated to deactivate commercial antibiotics.
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工程(英文)
ISSN: 2095-8099
Year: 2024
Issue: 12
Volume: 43
Page: 216-227
1 0 . 1 0 0
JCR@2023
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30 Days PV: 1
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