Antibiotic-resistant
bacteria are a severe threat to human health.
The World Health Organization’s Global Antimicrobial Surveillance
System has revealed widespread occurrence of antibiotic resistance
among half a million patients across 22 countries, with Staphylococcus aureus, Escherichia
coli, and Klebsiella pneumoniae being the most common resistant species. Antimicrobial nanoparticles
are emerging as a promising alternative to antibiotics in the fight
against antimicrobial resistance. In this work, selenium nanoparticles
coated with the antimicrobial polypeptide, ε-poly-l-lysine, (Se NP-ε-PL) were synthesized and their antibacterial
activity and cytotoxicity were investigated. Se NP-ε-PL exhibited
significantly greater antibacterial activity against all eight bacterial
species tested, including Gram-positive, Gram-negative, and drug-resistant
strains, than their individual components, Se NP and ε-PL. The
nanoparticles showed no toxicity toward human dermal fibroblasts at
the minimum inhibitory concentrations, demonstrating a therapeutic
window. Furthermore, unlike the conventional antibiotic kanamycin,
Se NP-ε-PL did not readily induce resistance in E. coli or S. aureus. Specifically, S. aureus began to develop resistance to kanamycin
from ∼44 generations, whereas it took ∼132 generations
for resistance to develop to Se NP-ε-PL. Startlingly, E. coli was not able to develop resistance to the
nanoparticles over ∼300 generations. These results indicate
that the multifunctional approach of combining Se NP with ε-PL
to form Se NP-ε-PL is a highly efficacious new strategy with
wide-spectrum antibacterial activity, low cytotoxicity, and significant
delays in development of resistance.