Potent antibacterial antisense peptide-peptide nucleic acid conjugates against Pseudomonas aeruginosa.
Nucleic Acid Ther
; 22(5): 323-34, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-23030590
ABSTRACT
Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections in hospital settings, especially with immune compromised patients, and the increasing prevalence of multidrug resistant strains urges search for new drugs with novel mechanisms of action. In this study we introduce antisense peptide-peptide nucleic acid (PNA) conjugates as antibacterial agents against P. aeruginosa. We have designed and optimized antisense peptide-PNA conjugates targeting the translation initiation region of the ftsZ gene (an essential bacterial gene involved in cell division) or the acpP gene (an essential bacterial gene involved in fatty acid synthesis) of P. aeruginosa (PA01) and characterized these compounds according to their antimicrobial activity and mode of action. Four antisense PNA oligomers conjugated to the H-(R-Ahx-R)(4)-Ahx-ßala or the H-(R-Ahx)(6)-ßala peptide exhibited complete growth inhibition of P. aeruginosa strains PA01, PA14, and LESB58 at 1-2 µM concentrations without any indication of bacterial membrane disruption (even at 20 µM), and resulted in specific reduction of the targeted mRNA levels. One of the four compounds showed clear bactericidal activity while the other significantly reduced bacterial survival. These results open the possibility of development of antisense antibacterials for treatment of Pseudomonas infections.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Oligonucleotídeos Antissenso
/
Ácidos Nucleicos Peptídicos
/
Peptídeos Penetradores de Células
/
Antibacterianos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acid Ther
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Dinamarca