Adaptive Laboratory Evolution Of Escherichia Coli Reveals Arduous Resistance Development To A Combination Of Three Novel Antimicrobial Compounds And To The Short Amp P9-4

Linda Citterio, Henrik Franzyk, Lone Gram

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    Abstract

    Antimicrobial peptides (AMPs) were for long considered as promising new antimicrobials since resistance was not expected. However, adaptive evolution experiments have demonstrated that bacteria may indeed develop resistance also to AMPs. However, we and others hypothesize that the risk of resistance development decreases when two or more compounds are combined as compared to single-drug treatments. The purpose of this study was to determine if resistance could develop in Escherichia coli ATCC 25922 to the peptidomimetic HF-1002 2 and the AMPs novicidin and P9-4. The mentioned compounds were applied alone and in a combination of three in an adaptive evolution approach. All the lineages exposed to HF-1002 2 and three out of four lineages exposed to novicidin adapted to 32 x MIC, after approximately 350 generations. Conversely, only one out of four lineages exposed to the combination reached adaptation to 32 x MIC. This shows that resistance to novicidin and HF-1002 2, administered alone, developed more easily than it occurred in lineages exposed to the combination of three drugs. This result further supports combinatorial treatment as a way to circumvent resistance development. Surprisingly, none of the lineages exposed to P9-4 was adapted to 32 x MIC. This indicates that this short-length antimicrobial peptide may be a promising candidate for further optimization for future application in clinical settings.
    Original languageEnglish
    Title of host publicationThe Danish Microbiological Society Annual Congress 2015 : Programme & Abstracts
    Place of PublicationCopenhagen
    Publication date2015
    Pages29-29
    Publication statusPublished - 2015
    EventThe Danish Microbiological Society Annual Congress 2015 - Eigtved's Pakhus, Copenhagen, Denmark
    Duration: 9 Nov 20159 Nov 2015

    Conference

    ConferenceThe Danish Microbiological Society Annual Congress 2015
    LocationEigtved's Pakhus
    CountryDenmark
    CityCopenhagen
    Period09/11/201509/11/2015

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