Combined antimicrobial effect of two peptide nucleic acids against and veterinary isolates.

Background: and 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 spp., including methicillin-resistant (MRSA) and methicillin-resistant (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 , were constructed, and their antibacterial activities were analyzed.

Objectives: This study analyzed the combined antibacterial effects of P-PNAs on and clinical isolates.

Methods: 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 and 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 spp. revealed isolates to be resistant to P-PNAs and 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.