Promoting the healing of methicillin-resistant Staphylococcus aureus-infected wound by a multi-target antimicrobial AIEgen of 6-Aza-2-- thiothymine-decorated gold nanoclusters

The use of conventional antibiotic therapies is in question owing to the emergence of drug-resistant pathogenic bacteria. Therefore, novel, highly efficient antibacterial agents to effectively overcome resistant bacteria are urgently needed. Accordingly, in this work, we described a novel class luminogen of 6-Aza-2-thiothymine-decorated gold nanoclusters (ATT-AuNCs) with aggregation-induced emission property that possessed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Scanning electron microscopy was performed to investigate the interactions between ATT-AuNCs and MRSA. In addition, ATT-AuNCs exhibited excellent ROS generation efficiency and could effectively ablate MRSA via their internalization to the cells. Finally, tandem mass tag-labeling proteome analysis was carried out to investigate the differential expression proteins in MRSA strains. The results suggested that ATT-AuNCs killed MRSA cells through altering the expression of multiple target proteins involved in DNA replication, aminoacyl-tRNA synthesis, peptidoglycan and arginine biosynthesis metabolism. Parallel reaction monitoring technique was further used for the validation of these proteome results. ATT-AuNCs could also be served as a wound-healing agent and accelerate the healing process. Overall, we proposed ATT-AuNCs could serve as a robust antimicrobial aggregation-induced emission luminogen (AIEgen) that shows the ability to alter the activities of multiple targets for the elimination of drugresistant bacteria.

Automated summary

This study presented a novel class of luminogen called 6-Aza-2-thiothymine-decorated gold nanoclusters (ATT-AuNCs) with aggregation-induced emission property, which demonstrated potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). By generating reactive oxygen species (ROS) and altering the expression of multiple target proteins in MRSA cells, ATT-AuNCs effectively eliminated MRSA. Additionally, ATT-AuNCs could serve as a wound-healing agent. Therefore, ATT-AuNCs are considered robust antimicrobial aggregation-induced emission luminogens (AIEgens) capable of targeting multiple pathways to eliminate drug-resistant bacteria.