A Novel Peptide Nucleic Acid against the Cytidine Monophosphate Kinase of S. aureus Inhibits Staphylococcal Infection In Vivo
| Autor: | Hyung Tae Lee, Jang Won Yoon, Jun Bong Lee, Se Kye Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus antisense Peptide bactericidal activity Inhibitory postsynaptic potential medicine.disease_cause Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Drug Discovery a murine model medicine Gene chemistry.chemical_classification Peptide nucleic acid lcsh:RM1-950 anti-staphylococcal infection Molecular biology cytidine monophosphate kinase 030104 developmental biology lcsh:Therapeutics. Pharmacology chemistry 030220 oncology & carcinogenesis Molecular Medicine peptide nucleic acid FtsA Conjugate |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 18, Iss, Pp 245-252 (2019) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | Here, we report a novel bactericidal peptide nucleic acid (PNA) that can induce the antisense effect on the cytidine monophosphate kinase (Cmk) of Staphylococcus aureus, a putative essential component for bacterial species. Based on the genome sequence of S. aureus N315, a set of PNA conjugates with a bacterial penetration peptide, (KFF)3K, were synthesized to target the seven potentially essential genes (cmk, deoD, ligA, smpB, glmU, pyrH, and ftsA) and further evaluated for their antibacterial properties in vitro as well as in vivo. The results demonstrated that two peptide-conjugated PNAs (P-PNAs), antisense P-PNA (ASP)-cmk1 and ASP-deoD1, targeting either the cmk or the deoD genes, had the strongest inhibitory effects on the growth of S. aureus ATCC 29740 (a bovine mastitic milk isolate) in a dose-dependent manner. In vivo application of ASP-cmk1 resulted in a significant reduction of bacterial loads in mice intraperitoneally infected with a sublethal dose of S. aureus. Moreover, ASP-cmk1 significantly increased the survival rate of the breast-fed infant mice after intramammary infection of the lactating CD-1 mice. Taken together, our characterization of ASP-cmk1 demonstrated its bactericidal activity against S. aureus as well as its effectiveness in vivo. Keywords: peptide nucleic acid, antisense, cytidine monophosphate kinase, Staphylococcus aureus, bactericidal activity, anti-staphylococcal infection, a murine model |
| Databáze: | OpenAIRE |
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