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Drug-Free Enzyme-Based Bactericidal Nanomotors against Pathogenic Bacteria.

ABSTRACT: The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic Escherichia coli. U-MSNPs exhibited the highest bactericidal activity due to biocatalysis of urea into NaHCO₃ and NH₃, which also propels U-MSNPs. In addition, U-MSNPs in concentrations above 200 μg/mL were capable of successfully reducing 60% of the biofilm biomass of a uropathogenic E. coli strain. This study thus provides a proof-of-concept, demonstrating that enzyme-based nanomotors are capable of fighting infectious diseases. This approach could potentially be extended to other kinds of diseases by selecting appropriate biomolecules.

SUBMITTER: Vilela D

PROVIDER: S-EPMC8478280 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Drug-Free Enzyme-Based Bactericidal Nanomotors against Pathogenic Bacteria.

Vilela Diana D Blanco-Cabra Nuria N Eguskiza Ander A Hortelao Ana C AC Torrents Eduard E Sanchez Samuel S

ACS applied materials & interfaces 20210326 13

The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic <i>Escherich ...[more]

PMID: 33769023

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Project description:We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal activities of the resultant SC4 'peptide-amphiphile' molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), including S. aureus strains resistant to conventional antibiotics, but little or no increase in bactericidal activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fatty acid conjugation improved endotoxin (lipopolysaccharide) neutralization by 3- to 6-fold. Although acylation somewhat increased lysis of human erythrocytes, it did not increase lysis of endothelial cells, and the haemolytic effects occurred at concentrations 10- to 100-fold higher than those required for bacterial cell lysis. For insight into the mechanism of action of SC4 peptide-amphiphiles, CD, NMR and fluorescence spectroscopy studies were performed in micelle and liposome models of eukaryotic and bacterial cell membranes. CD indicated that SC4 peptide-amphiphiles had the strongest helical tendencies in liposomes mimicking bacterial membranes, and strong membrane integration of the SC4 peptide-amphiphiles was observed using tryptophan fluorescence spectroscopy under these conditions; results that correlated with the increased bactericidal activities of SC4 peptide-amphiphiles. NMR structural analysis in micelles demonstrated that the two-thirds of the peptide closest to the fatty acid tail exhibited a helical conformation, with the positively-charged side of the amphipathic helix interacting more with the model membrane surface. These results indicate that conjugation of a fatty acid chain to the SC4 peptide enhances membrane interactions, stabilizes helical structure in the membrane-bound state and increases bactericidal potency.

Project description:Antibiotic-resistant pathogenic bacteria and the oxidative stress related to their infections are dangerous health problems. Finding new safe, effective antibacterial and antioxidant agents is an urgent global need. Probiotics are a strong candidate for possible antibacterial and antioxidant agents. The delivery of these probiotics without any effect on gastrointestinal digestion is the most important point for their application. The encapsulation of the probiotics on nanoparticles or other supports is a well-known method for the safe delivery of the probiotics. Little information is known about the effect of the probiotic encapsulation on its antibacterial and antioxidant activity. The present study tried to investigate the effect of probiotic encapsulation on nano-chitosan on its antioxidant activity and antibacterial activity against some pathogenic bacteria. We encapsulated some known probiotic species on nano-chitosan and investigated the antibacterial activity of the nano-probiotics and free probiotics against gastrointestinal pathogenic bacteria. The antioxidant characters of the free and encapsulated probiotics were investigated in terms of DPPH radicle scavenging activity, ferric ion chelating activity, hydroxyl radicle scavenging activity, superoxide anion radicle scavenging activity, and anti-lipid peroxidation activity. Results showed the superiority of the encapsulated probiotics as antibacterial and antioxidant agents over the free ones. The encapsulation improved the antibacterial activity of Sporolactobacillus laevolacticus against Bacteroides fragilis by 134% compared to the free one. Also, significantly, the encapsulation increased the hydroxyl radicle scavenging activity of Enterococcus faecium by about 180% compared to the free one. Nano-chitosan encapsulation synergistically increased the antioxidant and antibacterial activity of the studied probiotics. This can be promising for controlling pathogenic bacteria.Supplementary informationThe online version contains supplementary material available at 10.1007/s12088-023-01140-2.

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Drug-Free Enzyme-Based Bactericidal Nanomotors against Pathogenic Bacteria.

Publications

Drug-Free Enzyme-Based Bactericidal Nanomotors against Pathogenic Bacteria.

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