DNA scaffolds organize silver nanoclusters into potent antimicrobials that precisely kill antibiotic-resistant bacteria, including those causing meningitis.
(Nanowerk Spotlight) Antibiotic-resistant bacteria cause more than a million deaths each year, and their rapid evolution continues to undermine the effectiveness of newly developed drugs. Among these, ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, represent the most dangerous group, driving hospital-acquired infections and global mortality due to their ability to evade existing antibiotics. This growing crisis underscores the urgent need for alternative antimicrobial strategies.
Nanoscale silver has long been recognized for its antimicrobial properties; however, its clinical use is limited because effective doses often approach toxic levels. To overcome these challenges, a collaborative international team led by Kirill Afonin at UNC Charlotte has developed programmable, self-assembling DNA scaffolds that template, stabilize, and precisely organize multiple silver nanoclusters (DNA-AgNCs). This spatial organization enhances antimicrobial potency while imparting intrinsic fluorescence, enabling simultaneous therapeutic action and real-time optical tracking.
The team’s recent study published in ACS Applied Materials & Interfaces (“Spatially Organized DNA-Templated Silver Nanoclusters as Potent Antimicrobial Agents for ESKAPE Infections”) reports the design of spatially organized DNA-AgNCs integrated with nucleic acid nanostructures to create highly potent antimicrobial systems. By precisely arranging AgNCs on programmable DNA scaffolds, the researchers achieved enhanced local silver concentration and improved structural control, resulting in strong activity against clinically relevant, antibiotic-resistant ESKAPE pathogens.
Figure 1: Overview depicting the reduction of intra- and extra-cellular bacterial burden by DNA-AgNCs structures. (Image: Reproduced from DOI:10.1021/acsami.5c25898, CC BY)
Among the designs tested, cytosine-rich DNA hairpins (C13) produced the most stable and potent nanoclusters and linking multiple hairpins or assembling them into fibrous structures further enhanced antibacterial activity. These multivalent architectures delivered higher local silver concentrations, leading to significantly improved bacterial killing at low doses, often outperforming conventional antibiotics.
These DNA-AgNCs demonstrated strong efficacy against highly resistant pathogens, including MRSA, carbapenem-resistant A. baumannii, and multidrug-resistant P. aeruginosa, with up to ~78-fold greater potency than standard antibiotics. Mechanistically, their bactericidal activity is driven by the generation of reactive oxygen species, including singlet oxygen, along with disruption of bacterial membranes.
Importantly, they were also effective against intracellular S. aureus in primary murine osteoblasts, significantly reducing bacterial burden, an area where traditional antibiotics often fail. The nanoclusters remained stable for weeks and exhibited minimal cytotoxicity to mammalian cells at therapeutic doses.
Figure 2: This figure depicts the antibacterial capabilities of DNA-AgNCs against drug-resistant ESKAPE pathogens. (Image: Reproduced from DOI:10.1021/acsami.5c25898, CC BY) (click on image to enlarge)
In a complementary study published in ACS Applied Bio Materials (“DNA-Templated Silver Nanoclusters Demonstrate Potent Antimicrobial Activity Against the Clinically Relevant Pathogens, Neisseria meningitidis and Streptococcus pneumoniae“), the team further demonstrated that DNA-AgNCs are effective against meningitis-causing pathogens, including Neisseria meningitidis and Streptococcus pneumoniae. By comparing different DNA architectures, the researchers showed that nanocluster organization directly influences stability, silver loading, and biological activity. These systems achieved potent antimicrobial effects at low silver concentrations while also reducing inflammatory responses without detectable toxicity.
“Together, these studies establish that programmable nucleic acid scaffolds can precisely control the formation, spatial organization, and biological function of silver nanoclusters, enabling a new class of tunable, highly effective, and potentially safer antimicrobial nanotherapeutics capable of addressing antibiotic-resistant and intracellular infections” concludes Dr. Elizabeth Skelly, a first name author on both publications.
Source: Provided by the Afonin Lab at UNC Charlotte
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