Antisense PNA Accumulates in Escherichia coli and Mediates a Long Post-antibiotic Effect
| Autor: | Erik Jan Klok, Mehrdad Behmanesh, Abbas Nikravesh, Rikard Dryselius, Shan Goh, Omid R. Faridani, Majid Sadeghizadeh, Anita Ganyu, Liam Good, Rula Zain |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Peptide Nucleic Acids
Antimicrobial pharmacodynamics Cell Biology medicine.disease_cause Bacterial cell structure DNA Antisense Microbiology chemistry.chemical_compound Drug Discovery medicine Acyl Carrier Protein Escherichia coli Genetics Molecular Biology Pharmacology Microbial Viability Peptide nucleic acid Base Sequence Dipeptides Antimicrobial Anti-Bacterial Agents Acyl carrier protein Kinetics medicine.anatomical_structure chemistry Biochemistry biology.protein Molecular Medicine Efflux |
| Zdroj: | Molecular Therapy. 15(8):1537-1542 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/sj.mt.6300209 |
| Popis: | Antisense agents that target growth-essential genes display surprisingly potent bactericidal properties. In particular, peptide nucleic acid (PNA) and phosphorodiamidate morpholino oligomers linked to cationic carrier peptides are effective in time kill assays and as inhibitors of bacterial peritonitis in mice. It is unclear how these relatively large antimicrobials overcome stringent bacterial barriers and mediate killing. Here we determined the transit kinetics of peptide–PNAs and observed an accumulation of cell-associated PNA in Escherichia coli and slow efflux. An inhibitor of drug efflux pumps did not alter peptide–PNA potency, indicating a lack of active efflux from cells. Consistent with cell retention, the post-antibiotic effect (PAE) of the anti-acyl carrier protein (acpP) peptide–PNA was greater than 11 hours. Bacterial cell accumulation and a long PAE are properties of significant interest for antimicrobial development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|