Journalartikel

Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes


AutorenlistePatenge, Nadja; Pappesch, Roberto; Krawack, Franziska; Walda, Claudia; Abu Mraheil, Mobarak; Jacob, Anette; Hain, Torsten; Kreikemeyer, Bernd

Jahr der Veröffentlichung2013

ZeitschriftMolecular Therapy: Nucleic Acids

Bandnummer2

ISSN2162-2531

Open Access StatusGold

DOI Linkhttps://doi.org/10.1038/mtna.2013.62

VerlagCell Press


Abstract
While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e. g., macrolides, has increased. Taken together, these facts demand the development of novel therapeutic strategies. In this study, S. pyogenes growth was inhibited by application of peptide-conjugated antisense-peptide nucleic acids (PNAs) specific for the essential gyrase A gene (gyrA). Thereby, HIV-1 Tat peptide-coupled PNAs were more efficient inhibitors of streptococcal growth as compared with (KFF) 3K-coupled PNAs. Peptideanti-gyrA PNAs decreased the abundance of gyrA transcripts in S. pyogenes. Growth inhibition by antisense interference was enhanced by combination of peptide-coupled PNAs with protein-level inhibitors. Antimicrobial synergy could be detected with levofloxacin and novobiocin, targeting the gyrase enzyme, and with spectinomycin, impeding ribosomal function. The prospective application of carrier peptide-coupled antisense PNAs in S. pyogenes covers the use as an antimicrobial agent and the employment as a knock-down strategy for the investigation of virulence factor function.



Zitierstile

Harvard-ZitierstilPatenge, N., Pappesch, R., Krawack, F., Walda, C., Abu Mraheil, M., Jacob, A., et al. (2013) Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes, Molecular Therapy: Nucleic Acids, 2, Article e132. https://doi.org/10.1038/mtna.2013.62

APA-ZitierstilPatenge, N., Pappesch, R., Krawack, F., Walda, C., Abu Mraheil, M., Jacob, A., Hain, T., & Kreikemeyer, B. (2013). Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes. Molecular Therapy: Nucleic Acids. 2, Article e132. https://doi.org/10.1038/mtna.2013.62



Schlagwörter


ANTI-MICROBIAL COMBINATIONSANTISENSEANTISENSE INHIBITIONcell-penetrating peptidesCELL-PENETRATING PEPTIDESHIV-1 peptideNUCLEIC-ACIDSPNARHEUMATIC-FEVERStreptococcus pyogenes


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