title: Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes.
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. Peptide-anti-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.Molecular Therapy-Nucleic Acids (2013) 2, e132; doi:10.1038/mtna.2013.62; published online 5 November 2013.
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Center, Rostock, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Patenge
authors.forename: Roberto
authors.initials: R
authors.lastname: Pappesch
authors.forename: Franziska
authors.initials: F
authors.lastname: Krawack
authors.forename: Claudia
authors.initials: C
authors.lastname: Walda
authors.forename: Mobarak Abu
authors.initials: MA
authors.lastname: Mraheil
authors.forename: Anette
authors.initials: A
authors.lastname: Jacob
authors.forename: Torsten
authors.initials: T
authors.lastname: Hain
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer