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

Autor:	Olesk J; Department of Aerospace and Mechanical Engineering, University of Notre Dame Notre Dame Indiana USA pnallath@nd.edu +1 574 631 7868., Donahue D; W. M. Keck Center for Transgene Research, University of Notre Dame Notre Dame Indiana USA., Ross J; Department of Biological Sciences, University of Notre Dame Notre Dame Indiana USA., Sheehan C; Department of Chemistry and Biochemistry, University of Notre Dame Notre Dame Indiana USA., Bennett Z; Department of Aerospace and Mechanical Engineering, University of Notre Dame Notre Dame Indiana USA pnallath@nd.edu +1 574 631 7868., Armknecht K; Department of Pre-Professional Studies, University of Notre Dame Notre Dame Indiana USA., Kudary C; Berthiaume Institute for Precision Health, University of Notre Dame Notre Dame Indiana USA., Hopf J; Berthiaume Institute for Precision Health, University of Notre Dame Notre Dame Indiana USA., Ploplis VA; W. M. Keck Center for Transgene Research, University of Notre Dame Notre Dame Indiana USA., Castellino FJ; W. M. Keck Center for Transgene Research, University of Notre Dame Notre Dame Indiana USA., Lee SW; Department of Biological Sciences, University of Notre Dame Notre Dame Indiana USA., Nallathamby PD; Department of Aerospace and Mechanical Engineering, University of Notre Dame Notre Dame Indiana USA pnallath@nd.edu +1 574 631 7868.; Berthiaume Institute for Precision Health, University of Notre Dame Notre Dame Indiana USA.
Jazyk:	angličtina
Zdroj:	Nanoscale advances [Nanoscale Adv] 2024 Jan 10; Vol. 6 (4), pp. 1145-1162. Date of Electronic Publication: 2024 Jan 10 (Print Publication: 2024).
DOI:	10.1039/d3na00620d
Abstrakt:	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. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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