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        Species-selective killing of bacteria by antimicrobial peptide-PNAs

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        Author
        Mondhe, Madhav
        Chessher, Ashley
        Goh, Shan
        Good, Liam
        Stach, James E M
        Attention
        2299/19788
        Abstract
        Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.
        Publication date
        2014-02-18
        Published in
        PLoS ONE
        Published version
        https://doi.org/10.1371/journal.pone.0089082
        Other links
        http://hdl.handle.net/2299/19788
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