Issue 4, 2024

Antimicrobial peptide-conjugated phage-mimicking nanoparticles exhibit potent bactericidal action against Streptococcus pyogenes in murine wound infection models

Abstract

Streptococcus pyogenes is a causative agent for strep throat, impetigo, and more invasive diseases. The main reason for the treatment failure of streptococcal infections is increased antibiotic resistance. In recent years, infectious diseases caused by pyogenic streptococci resistant to multiple antibiotics have been rising with a significant impact on public health and the veterinary industry. The development of antibiotic resistance and the resulting emergence of multidrug-resistant bacteria have become primary threats to the public health system, commonly leading to nosocomial infections. Many researchers have turned their focus to developing alternative classes of antibacterial agent based on various nanomaterials. We have developed an antibiotic-free nanoparticle system inspired by naturally occurring bacteriophages to fight antibiotic-resistant bacteria. Our phage-mimicking nanoparticles (PhaNPs) display structural mimicry of protein-turret distribution on the head structure of bacteriophages. By mimicking phages, we can take advantage of their evolutionary constant shape and high antibacterial activity while avoiding the immune reactions of the human body experienced by biologically derived phages. We describe the synthesis of hierarchically arranged core–shell nanoparticles, with a silica core conjugated with silver-coated gold nanospheres to which we have chemisorbed the synthetic antimicrobial peptide Syn-71 on the PhaNPs surface, and increased the rapidity of the antibacterial activity of the nanoparticles (PhaNP@Syn71). The antibacterial effect of the PhaNP@Syn71 was tested in vitro and in vivo in mouse wound infection models. In vitro, results showed a dose-dependent complete inhibition of bacterial growth (>99.99%). Cytocompatibility testing on HaCaT human skin keratinocytes showed minimal cytotoxicity of PhaNP@Syn71, being comparable to the vehicle cytotoxicity levels even at higher concentrations, thus proving that our design is biocompatible with human cells. There was a minimum cutoff dosage above which there was no evolution of resistance after prolonged exposure to sub-MIC dosages of PhaNP@Syn71. Application of PhaNP@Syn71 to a mouse wound infection model exhibited high biocompatibility in vivo while showing immediate stabilization of the wound size, and infection free wound healing. Our results suggest the robust utility of antimicrobial peptide-conjugated phage-mimicking nanoparticles as a highly effective antibacterial system that can combat bacterial infections consistently while avoiding the emergence of resistant bacterial strains.

Graphical abstract: Antimicrobial peptide-conjugated phage-mimicking nanoparticles exhibit potent bactericidal action against Streptococcus pyogenes in murine wound infection models

Supplementary files

Article information

Article type
Paper
Submitted
08 aug 2023
Accepted
08 jan 2024
First published
10 jan 2024
This article is Open Access
Creative Commons BY-NC license

Nanoscale Adv., 2024,6, 1145-1162

Antimicrobial peptide-conjugated phage-mimicking nanoparticles exhibit potent bactericidal action against Streptococcus pyogenes in murine wound infection models

J. Olesk, D. Donahue, J. Ross, C. Sheehan, Z. Bennett, K. Armknecht, C. Kudary, J. Hopf, V. A. Ploplis, F. J. Castellino, S. W. Lee and P. D. Nallathamby, Nanoscale Adv., 2024, 6, 1145 DOI: 10.1039/D3NA00620D

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements