Multifunctional Antimicrobial Polypeptide-Selenium Nanoparticles Combat Drug-Resistant Bacteria

Abstract

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.

The Advancing of Selenium Nanoparticles Against Infectious Diseases

“…Huang et al reported that Se NPs exhibited strong antibacterial activity against eight bacterial species, including Gram-positive, Gram-negative, and drug-resistant strains (Huang et al, 2020). Furthermore, unlike the conventional antibiotic kanamycin, Se NPs did not readily induce resistance in E. coli or S. aureus, indicating the potential use of Se NPs to delay drug resistance.…”

Selenium Nanoparticles as Candidates for Antibacterial Substitutes and Supplements against Multidrug-Resistant Bacteria

“…Among them, selenium nanoparticles (SeNPs) have attracted increased attention. Selenium (Se) is an essential trace element for humans (about 50 µg/day), and antimicrobial studies using different forms of Se, such as selenite and SeNPs, have been reported [28][29][30][31][32][33]. Se is a significant element, because it is an important cofactor for antioxidant enzymes such as glutathione peroxidase and thioredoxin reductase [34,35].…”

Selenite Reduction by Proteus sp. YS02: New Insights Revealed by Comparative Transcriptomics and Antibacterial Effectiveness of the Biogenic Se0 Nanoparticles

“…These results could be attributed to the distinct differences in the cell wall structure/cell surface between Gram-positive and Gram-negative bacteria—the former have a stronger molecular network in the cell wall, which could present more difficulties for selenite ions to penetrate the cell than in Gram-negative bacteria ( Truong et al, 2021 ). It has recently been reported that the bactericidal activity of SeNPs can be explained in terms of changing the membrane potential, depleting ATP, promoting ROS production, and disrupting the membrane ( Huang et al, 2020 ).…”