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        Antisense PNA accumulates in Escherichia coli and mediates a long post-antibiotic effect

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        Author
        Nikravesh, Abbas
        Dryselius, Rikard
        Faridani, Omid R
        Goh, Shan
        Sadeghizadeh, Majid
        Behmanesh, Mehrdad
        Ganyu, Anita
        Klok, Erik Jan
        Zain, Rula
        Good, Liam
        Attention
        2299/20676
        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.
        Publication date
        2007-08-01
        Published in
        Molecular therapy : the journal of the American Society of Gene Therapy
        Published version
        https://doi.org/10.1038/sj.mt.6300209
        License
        http://creativecommons.org/licenses/by/4.0/
        Other links
        http://hdl.handle.net/2299/20676
        Relations
        School of Life and Medical Sciences
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