Designing Self‐Assembling Chimeric Peptide Nanoparticles with High Stability for Combating Piglet Bacterial Infections

Abstract

As a novel type of antibiotic alternative, peptide‐based antibacterial drug shows potential application prospects attributable to their unique mechanism for lysing the membrane of pathogenic bacteria. However, peptide‐based antibacterial drugs suffer from a series of problems, most notably their immature stability, which seriously hinders their application. In this study, self‐assembling chimeric peptide nanoparticles (which offer excellent stability in the presence of proteases and salts) are constructed and applied to the treatment of bacterial infections. In vitro studies are used to demonstrate that peptide nanoparticles NPs1 and NPs2 offer broad‐spectrum antibacterial activity and desirable biocompatibility, and they retain their antibacterial ability in physiological salt environments. Peptide nanoparticles NPs1 and NPs2 can resist degradation under high concentrations of proteases. In vivo studies illustrate that the toxicity caused by peptide nanoparticles NPs1 and NPs2 is negligible, and these nanoparticles can alleviate systemic bacterial infections in mice and piglets. The membrane permeation mechanism and interference with the cell cycle differ from that of antibiotics and mean that the nanoparticles are at a lower risk of inducing drug resistance. Collectively, these advances may accelerate the development of peptide‐based antibacterial nanomaterials and can be applied to the construction of supramolecular nanomaterials.

Wickerhamomyces anomalus relieves weaning diarrhea via improving gut microbiota and redox homeostasis using a piglet model

“…However, the overuse of antibiotics caused a series of social issues threatening human health, such as the emergence of multi-drug resistant bacteria, drug residues in meat products, and environmental pollution. [3][4][5] As a result, many countries have restricted and banned the use of antibiotics in animal husbandry. 6 Therefore, under the pressure of restricting the use of antibiotics, nutritionists need to seek safe and effective alternatives to antibiotics.…”

Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

“…28 Arginine (Arg) guanidine side chain can generate bidentate hydrogen bonds with the phosphate group of lipids, thereby giving the peptide nanofibers stronger ability to penetrate bacterial membranes. 22 Therefore, we have introduced eight Arg residues to provide positive charges to the peptide chain in PCBP and acetylate at the carbonyl terminus of PCBP. 29 In addition, the incorporation of aromatic amino acids such as Phe is beneficial for the peptide nanofibers to enter the bacterial membrane, and the mutual attractions between Phe and positive and negative charges are conducive to inducing the co-assembly of peptide chains, thereby improving the assembly ability of supramolecular nanofibers.…”

“…Finally, the samples were stained with H&E for histological analysis. 51,52 4.19. Activity Assessment In Vivo.…”

“…In this study, we designed positively charged bactericidal peptide (PCBP) and negatively charged attenuating peptide (NCAP) based on the structure–function relationship approach. PCBP consists of three distinct domains: (i) a hydrophobic unit composed of carbon alkyl chains that provide peptides with the necessary hydrophobicity and assembly power for sterilization; (ii) three repeating phenylalanine–lysine–phenylalanine sequences (FKF), which enhance the ability of peptide assembly by utilizing the force between aromatic amino acids and the mutual attraction of positive and negative charges; and (iii) eight positively charged arginine (Arg) as bactericidal domains to ensure that the nanofibers have an electrostatic binding effect on bacterial membranes . Finally, acetamidation at the end of PCBP adds a charge .…”

Intramembrane Nanoaggregates of Antimicrobial Peptides Play a Vital Role in Bacterial Killing

“…Further issues with long sequences lie in their vulnerability to enzymatic degradation, cost of synthesis, purification, and control of their secondary structures in product formulation. [8][9][10][11] Natural AMPs that have been extensively studied include Melittin, derived from bee venom, Maginin-2 from frog skin, and Cathelicidin LL-37 from human tissues. [12][13][14] These natural AMPs and their mimetics, such as Pexiganan, have shown a wide range of efficacy against both Gram-positive and Gramnegative bacteria.…”