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Author Spotlight: Metallic Nanocomposites to Eliminate Antibiotic-Resistant Bacteria
Published on: October 4, 2024
Shikonin-copper coordination nanoparticles for enhanced antibacterial and antibiofilm activity against Staphylococcus
Yourang Jiang1, Xueyong Tang1, Ailin Wang1
1Chongqing Clinical Research Center for Dermatology, Chongqing Key Laboratory of Integrative Dermatology Research, Key Laboratory of External Therapies of Traditional Chinese Medicine in Eczema, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital/The First Affiliated Hospital of Chongqing College of Traditional Chinese Medicine, Chongqing, 400011, China.
Abstract:
Antimicrobial resistance (AMR) poses a critical global health challenge, with an estimated 1.27 million AMR-attributable deaths in 2019 and projections of 39 million cumulative deaths from 2025 to 2050, particularly driven by Staphylococcus aureus and methicillin-resistant strains (MRSA) that form robust biofilms conferring up to 1000-fold antibiotic tolerance and complicating hospital-acquired infections. Here, we report a green, one-pot synthesis of shikonin-copper nanoparticles (SCu NPs), employing shikonin (SK)-a naphthoquinone from Lithospermum erythrorhizon roots-as a dual chelator and stabilizer, without exogenous reductants or surfactants; density functional theory (DFT) computations guide the design, predicting thermodynamically favored 1:2 Cu(II): SK stoichiometry, yielding stable spherical nanoparticles (39.25 ± 3.24 nm) with preserved Cu(II) oxidation state, as validated by TEM, XPS, XRD, and UV-Vis spectroscopy. SCu NPs exhibit potent antibacterial activity against S. aureus ATCC 25,923, with minimum inhibitory and bactericidal concentrations (MIC/MBC) of 4/8 µg/mL-half those of SK (8/16 µg/mL)-and rapid bactericidal kinetics, reducing viability by 66% within 2 h; antibiofilm assays reveal concentration-dependent inhibition, achieving up to 89% biomass reduction at 32 µg/mL, outperforming SK, CuSO4, and their mixture, with SEM confirming extensive membrane disruption and cytoplasmic leakage. This synergy arises from Cu(II)-mediated reactive oxygen species (ROS) generation, enhanced lipophilicity, and SK's quorum-sensing inhibition, positioning SCu NPs as a sustainable, multi-target platform integrating natural product chemistry and nanotechnology to combat biofilm-associated AMR, mitigate resistance emergence, and advance therapeutics for recalcitrant infections.
Insights
Researchers developed shikonin-copper nanoparticles (SCu NPs) for antimicrobial resistance (AMR). These nanoparticles show potent antibacterial and antibiofilm activity against Staphylococcus aureus, offering a novel therapeutic strategy.
Area of Science:
- Nanotechnology and Materials Science
- Microbiology and Infectious Diseases
- Natural Product Chemistry
Background:
- Antimicrobial resistance (AMR) is a global health crisis, with Staphylococcus aureus (MRSA) biofilms causing significant mortality and hospital-acquired infections.
- Existing treatments face challenges due to high antibiotic tolerance in biofilms, necessitating novel therapeutic approaches.
- Shikonin (SK), a natural naphthoquinone, and copper ions show antimicrobial potential but require optimized delivery systems.
Purpose of the Study:
- To develop a green, one-pot synthesis of shikonin-copper nanoparticles (SCu NPs) for combating AMR.
- To evaluate the antibacterial and antibiofilm efficacy of SCu NPs against Staphylococcus aureus.
- To elucidate the synergistic mechanisms underlying the activity of SCu NPs.
Main Methods:
- Green synthesis of SCu NPs using shikonin as a chelator and stabilizer, guided by DFT calculations.
- Characterization of SCu NPs using TEM, XPS, XRD, and UV-Vis spectroscopy.
- Assessment of antibacterial activity (MIC/MBC, kinetics) and antibiofilm efficacy via biomass reduction assays and SEM imaging.
Main Results:
- Successfully synthesized stable, spherical SCu NPs (39.25 ± 3.24 nm) with preserved Cu(II) oxidation state.
- SCu NPs demonstrated potent antibacterial activity against S. aureus (MIC/MBC 4/8 µg/mL), outperforming shikonin alone.
- SCu NPs significantly inhibited biofilm formation (up to 89% biomass reduction) and disrupted bacterial membranes, superior to individual components.
Conclusions:
- SCu NPs represent a sustainable, multi-target platform for combating biofilm-associated AMR.
- The synergistic action involves ROS generation, enhanced lipophilicity, and quorum-sensing inhibition.
- This nanotechnology-based approach holds promise for treating recalcitrant infections and mitigating resistance emergence.

