Abstract
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.
Original language | English |
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Pages (from-to) | 1537-42 |
Number of pages | 6 |
Journal | Molecular therapy : the journal of the American Society of Gene Therapy |
Volume | 15 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Aug 2007 |
Keywords
- Acyl Carrier Protein
- Anti-Bacterial Agents
- Base Sequence
- DNA, Antisense
- Dipeptides
- Escherichia coli
- Kinetics
- Microbial Viability
- Peptide Nucleic Acids
- Journal Article
- Research Support, Non-U.S. Gov't