Nonantibiotic small molecule-modified gold nanoparticles (Au NPs) show great potential as an alternative for commercial antibiotics, yet their narrow antibacterial spectrum hinders the wide application in clinics. We observe that Au NPs cofunctionalized with both bovine serum albumin (BSA) and 4,6-diamino-2-pyrimidinethiol (DAPT) can generate conjugates (Au_DAPT_BSA) with progressive antimicrobial activities, including decreased minimal inhibitory concentration against Gram-negative bacteria and extended antibacterial spectrum against Gram-positive bacteria compared with DAPT-capped Au NPs (Au_DAPT). Au_DAPT_BSA induces no drug resistance and can significantly decrease the number of bacteria in the biofilms formed by Pseudomonas aeruginosa and Staphylococcus aureus. In addition, Au_DAPT_BSA exhibit in vivo healing efficiency for mice with subcutaneous abscesses caused by clinically isolated, multidrug resistant Escherichia coli or S. aureus without inducing detectable toxicity to the mammalian cells/animals. Our findings provide a new strategy for strengthening nanomaterial-based bactericides such as Au NPs, especially against drug-resistant bacterial infections.
Keywords: bactericide; drug-resistant infection; gold nanoparticles; non-antibiotic molecule; protein.