Amphiphilic silver nanoclusters show active nano–bio interaction with compelling antibacterial activity against multidrug-resistant bacteria

Abstract

Multidrug resistance represents a growing threat to human beings, and alternative antimicrobial regimens to conventional antibiotic paradigms are being extensively searched to fight against multidrug-resistant bacteria (MDRB). Although the antimicrobial potency of silver nanomaterials (AgNMs) has been previously elaborated, their efficacy against MDRB still remains to be strengthened. Here, our data revealed that small-sized silver nanoclusters (AgNCs) are superior to conventional silver nanoparticles (AgNPs) as robust antimicrobials against multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). The core structure and surface ligands of AgNCs are crucial for the outstanding antibacterial activity of AgNCs. On the one hand, due to the presence of amphiphilic ligands, AgNCs are relatively prone to associate with the cell membrane and partake in endocytosis with targeted bacterial cells. Molecular dynamics simulations also corroborated this finding. On the other hand, the nanocluster structure of AgNCs led to strong peroxidase-like activity associated with massive production of reactive oxygen species (ROS), which contributes to their overall bactericidal potency. These outstanding features of AgNCs result in elevated bacterial killing efficacy by impairing the cell wall/membrane, promoting oxidative stress and attenuating pivotal cellular processes, e.g., ATP synthesis. Notably, AgNCs manifested great efficacy in treating P. aeruginosa-generated pneumonia in mice and increased the survival of infected animals, as well as exhibited excellent biocompatibility. Taken together, the results of this study pinpoint the great promise of AgNCs as new alternative therapeutics against MDR P. aeruginosa.

DNA-Templated Silver Nanoclusters as Dual-Mode Sensitive Probes for Self-Powered Biosensor Fueled by Glucose

“…In addition to the many reports on their optical properties, other properties of AgNCs@DNA associated with the unique structure of electronic states have been reported. For example, antibacterial activity has been recently reported, which was discussed in connection with a distinct color change, a unique charge state of AgNCs@DNA leading to the production of free radicals and possibly singlet oxygen [29][30][31]. Researchers have also used phenomena such as guanine-rich DNA sequence-activated fluorescence enhancement [28,[32][33][34], aggregation-induced emission (AIE) [35], and photoinduced electron transfer (PET) [36] to design biosensing strategies using silver nanoclusters.…”

Homobifunctional imidoester-modified zinc nano-spindle attenuated hyphae growth of Aspergillus against hypersensitivity responses

“… 18 , 19 , 20 Cumulating in vitro evidence suggests that many of these biomaterial interactions result in synergistic antimicrobial effects with antibiotics (a positive side effect). 21 , 22 , 23 The proposed general mechanisms for the ability of nanomaterials to overcome antimicrobial resistance include the following: (1) Membrane damage: nanomaterials tend to rupture the cell membrane and damage the cell structure 24 , 25 , 26 ; (2) reactive oxygen species production: many nanomaterials induce the production of reactive oxygen species, which impair microbial metabolism and damage protein, membrane lipids, and DNA 26 ; (3) ion dissolution: released ions, such as silver ions, could attack biomolecules (e.g., thiol-rich proteins) directly 18 , 27 ; (4) enzyme-mimicking performance: the peroxidase-like activity of nanomaterials, such as palladium nanocrystals and iron oxide, enhances their bactericidal properties; and (5) biofilm eradication: some metal oxide nanoparticles can eradicate biofilms because of their strong redox reaction capabilities that perturb the cell metabolism. 24 , 25 , 26 However, antifungal prophylaxis is linked to drug-resistant fungal infections and probably results in disruption of the microbiota balance.…”

“…These fungi could invade the bloodstream and cause fatal invasive fungal infections (a negative side effect). 24 , 25 , 26 Moreover, several techniques using metal oxide nanoparticles in various biomedical sciences have been studied that have a great expectation on prevention and therapy of infections 20 , 28 …”

Antibiotic resistant bacteria: A bibliometric review of literature

“…The combination of antibiotics has a synergistic effect, which not only has better efficacy than a single drug, but also can inhibit the drug resistance selection of a single drug ( 45 , 46 ). With the development of multi-drug resistant bacteria, antibiotic substitutes ( 47 ) such as phage therapy ( 48 – 50 ), nanomaterials ( 51 – 54 ), bacteriocins ( 55 ), antibodies, and probiotics ( 56 ) have been attracted more attention.…”