Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
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Combined antimicrobial effect of two peptide nucleic acids against Staphylococcus aureus and S. pseudintermedius veterinary isolates

  • Se Kye Kim (College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University) ;
  • Jun Bong Lee (College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University) ;
  • Hyung Tae Lee (Quratis Inc.) ;
  • Jang Won Yoon (College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University)
  • Received : 2023.10.24
  • Accepted : 2023.12.17
  • Published : 2024.01.31
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Abstract

Background: Staphylococcus aureus and S. pseudintermedius are the major etiological agents of staphylococcal infections in humans, livestock, and companion animals. The misuse of antimicrobial drugs has led to the emergence of antimicrobial-resistant Staphylococcus spp., including methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. pseudintermedius (MRSP). One novel therapeutic approach against MRSA and MRSP is a peptide nucleic acid (PNA) that can bind to the target nucleotide strands and block expression. Previously, two PNAs conjugated with cell-penetrating peptides (P-PNAs), antisense PNA (ASP)-cmk and ASP-deoD, targeting two essential genes in S. aureus, were constructed, and their antibacterial activities were analyzed. Objectives: This study analyzed the combined antibacterial effects of P-PNAs on S. aureus and S. pseudintermedius clinical isolates. Methods: S. aureus ATCC 29740 cells were treated simultaneously with serially diluted ASP-cmk and ASP-deoD, and the minimal inhibitory concentrations (MICs) were measured. The combined P-PNA mixture was then treated with S. aureus and S. pseudintermedius veterinary isolates at the determined MIC, and the antibacterial effect was examined. Results: The combined treatment of two P-PNAs showed higher antibacterial activity than the individual treatments. The MICs of two individual P-PNAs were 20 and 25 µM, whereas that of the combined treatment was 10 µM. The application of a combined treatment to clinical Staphylococcus spp. revealed S. aureus isolates to be resistant to P-PNAs and S. pseudintermedius isolates to be susceptible. Conclusions: These observations highlight the complexity of designing ASPs with high efficacy for potential applications in treating staphylococcal infections in humans and animals.

Keywords

Acknowledgement

The S. aureus and S. pseudintermedius veterinary isolates used in this study were kind gifts from Prof. Soo Jin Yang in the College of Veterinary Medicine, Seoul National University.

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