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To tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH 2 –AgNPs) were  bactericidal ; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate–AgNPs) were  nontoxic ; and Ag +  ions were  bacteriostatic  forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in  E. coli . Further, adherent fimbriae were expressed with Citrate–AgNPs (0.5–10 µg/mL), whereas NH 2 –AgNPs (0.5–10 µg/mL) or Ag +  ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH 2 –AgNPs treatments, suggesting NH 2 –AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH 2 –AgNPs and the lack of toxicity of Citrate–AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.

Five nanometer size highly positive silver nanoparticles are bactericidal targeting cell wall and adherent fimbriae expression