Copper Clusters: An Effective Antibacterial for Eradicating Multidrug‐Resistant Bacterial Infection In Vitro and In Vivo

Abstract

Infections caused by multidrug-resistant (MDR) bacteria pose a threat to human health worldwide, making new effective antibacterial agents urgently desired. To date, it is still a great challenge to develop new antibiotics for MDR bacteria with clear antibacterial mechanisms. Herein, a novel alternative antibacterial copper clusters (CuCs) molecule is precisely synthesized utilizing an artificially designed theanine peptide. The prepared CuCs exhibit excellent broad-spectrum antibacterial activity in vitro, including gram-positive bacteria (methicillin-resistant Staphylococcus aureus [MRSA], Staphylococcus aureus, and Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The robust antibacterial effect is due to its ability to not only destroy the bacterial wall structure, but also regulate the ratio of GSH/GSSG by inhibiting the activity of glutathione reductase, thus causing the outbreak of reactive oxygen species and ultimately leading to bacterial death. In addition, in vivo studies demonstrate that CuCs can significantly rescue skin wound infections and sepsis in mice caused by MRSA, and has the same therapeutic efficacy as mupirocin ointment and first-line clinically anchored anti-MRSA drug vancomycin. Moreover, CuCs exhibit extremely low cytotoxicity to normal mammalian cells compared to silver and platinum clusters. With further development and optimization, CuCs has great potential as a new class of antibacterial agents to fight antibiotic-resistant pathogens.

Dual functions of epigallocatechin gallate surface-modified Au nanorods@selenium composites for near-infrared-II light-responsive synergistic antibacterial therapy

“…The antibacterial activity of the ASE NPs was also observed by a live/dead cell assay using SYTO@9 and PI fluorescent dye. Green/red bacterial cells were considered to be live/ dead cells with intact/damaged membranes, 47 which is a direct reflection of bacterial death. Fluorescence assays were performed by 488 nm laser excitation and 530 nm emission filters for SYTO 9 (live staining).…”

Advances in Nanostructures for Antimicrobial Therapy

“…Cu clusters prepared using an artificially designed theanine peptide exhibited strong in vitro antibacterial effects against MRSA, S. aureus, S. epidermidis , E. coli and P. aeruginosa due to the destruction of the bacterial wall structure and inhibition of the activity of glutathione reductase associated with ROS outburst, which can result in bacterial death. An in vivo study using Cu clusters revealed their beneficial impact on healing skin wound infections and sepsis caused by MRSA in mice, achieving therapeutic effectiveness comparable with that of mupirocin ointment and VAN along with very low cytotoxicity to normal mammalian cells [ 300 ].…”

Antibiotic-free antimicrobial poly (methyl methacrylate) bone cements: A state-of-the-art review

“…Third, there are number of novel antimicrobial materials that should be investigated for their suitability to be formulated into a suitable form to be used as additives for an AFAMBC. Examples of materials that could be added to the powder of a plain cement are a quorum-sensing inhibitor drug[ 113 ], Ti-doped ZnO[ 114 ], nano-GO nanosheets[ 115 ], selenium nanoparticles[ 116 ], Ag-nanoparticle-reduced GO nanocomposite[ 117 ], chitosan hybrid nanoparticles[ 118 ], a Cu cluster molecule[ 119 ], powder prepared from extract from a Tunisian lichen[ 120 ], Yb-doped ZnO nanoparticles[ 121 ], and an analog of PKZ18 (PKZ18-22), a molecule that has been shown to block growth of antibiotic-resistant S. aureus in biofilm[ 122 ]. Examples of materials that could be added to the liquid of a plain cement are benzothiazole or one of its derivatives[ 123 , 124 ] and a natural antimicrobial agent (such as extract of Salvadora persica , Olea europaea , and Ficus carcia leaves[ 125 ] or biosynthesized ZnO nanoflowers[ 126 ]).…”