Antimicrobial Cluster Bombs: Silver Nanoclusters Packed with Daptomycin

Abstract

Integration of two distinctive bactericides into one entity is a promising platform to improve the efficiency of antimicrobial agents. We report an efficient antimicrobial hybrid formed through conjugating silver nanoclusters (AgNCs) with daptomycin. The as-designed antimicrobial hybrid (D-AgNCs) inherits intrinsic properties of both bactericides with an enhanced synergistic performance. In particular, the chemically integrated D-AgNCs showed improved bacterial killing efficiency over the physically mixed daptomycin and AgNCs (D+AgNCs). More interestingly, the as-designed D-AgNCs could effectively damage the bacterial membrane. Propidium iodide (PI) stain showed bacterial membrane damage in about 85% of the bacteria population after treatment with D-AgNCs through creation of larger pores on the membrane as compared to D+AgNCs, largely due to the localization of daptomycin within the hybrid structure. These larger pores facilitated the entry of the D-AgNCs into the cell and led to more severe DNA damage of the bacterial DNA as compared to D+AgNCs in genomic DNA PAGE analysis. TUNEL assay further depicted more bacterial DNA breaks induced by D-AgNCs. The RecA gene expression level was upregulated, suggestive of DNA repair activation. The strong induced DNA damage benefited from the localization of AgNCs in the core of the antimicrobial hybrid structure, which could generate localized high ROS concentration and work as a critical ROS reservoir to continually generate ROS within the bacterium. The continual bombardments by these ROS generators restrict the ability of the bacteria to now develop resistance against this.

Antibacterial Activity of Silver Nanoparticles: Structural Effects

“…[83,84] However, as with chemo drugs, the toxicity effect of AgNPs can be used as a strategy against cancer cells and tumors. [86][87][88][89][90] Eventually, with these fundamental understandings of structural-antibacterial activities, we believe more potent AgNPs can be developed by precise control of their size, shape, and surface chemistry, which are expected to achieve with recent breakthroughs in the precision nanochemistry. These Ag nanomaterials possess an ultrasmall hydrodynamic diameter (HD) (below 5.5 nm, kidney filtration threshold) and thus can be rapidly cleared out of body in a reasonable time period through the urinary system, which can significantly reduce the risk of long-term cytotoxicity.…”

“…These Ag nanomaterials possess an ultrasmall hydrodynamic diameter (HD) (below 5.5 nm, kidney filtration threshold) and thus can be rapidly cleared out of body in a reasonable time period through the urinary system, which can significantly reduce the risk of long-term cytotoxicity. [86][87][88][89][90] Eventually, with these fundamental understandings of structural-antibacterial activities, we believe more potent AgNPs can be developed by precise control of their size, shape, and surface chemistry, which are expected to achieve with recent breakthroughs in the precision nanochemistry. Figure 6.…”

Cholesterol-Assisted Bacterial Cell Surface Engineering for Photodynamic Inactivation of Gram-Positive and Gram-Negative Bacteria

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 (2) It has been shown that nanoagents can easily enter bacterial cells after their membranes are damaged. 69 …”

Emerging 0D Transition‐Metal Dichalcogenides for Sensors, Biomedicine, and Clean Energy

“…Much improved or novel properties arise as a consequence of edge and quantum confinement effects, while the inherent merits derived from their corresponding 2D parents are still preserved . Up to now, 0D nanostructures, such as metal nanoparticles and nanoclusters, metal sulfide quantum dots (QDs), and carbon nanodots (NDs), are well reported with unabated interest. Compared to their native 2D forms, these new classes of 0D materials exhibit even smaller sizes, higher surface‐to‐volume ratios, more edge sites to be activated and functionalized ( Figure ) …”