Developing Membrane Targeting Antimicrobial Lipo-Peptoids by Modular Peptidomimicry and High Throughput Imaging

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According to the World Health Organization, antimicrobial resistance (AMR) is one of the gravest threats to public health, causing already 33,000 lives lost in Europe p.a. and more globally, as well as lost productivity and increased healthcare costs. Developing new antimicrobials is an important tool for combating AMR, but discovering molecules with high selectivity for microbes (i.e. low toxicity for humans) is difficult. Moreover, typical biological assay and microscopy screening tools for identifying novel antimicrobials have a trade-off between screening efficiency and providing sufficient information to inform mechanistic understanding for driving innovation. In this project we aim to take advantage of a novel high speed, high resolution microscopy technique to fundamentally improve the quality and throughput of screening a new class of peptide-mimetic antimicrobials. In particular, preliminary results show that our "membrane targeting antimicrobial (lipo)peptoids" (mTAPs) should enable flexible modulation of antimicrobial activity and cell toxicity. Successful identification of a novel class of targeting antimicrobials and its subsequent development will be of great interest to both the pharmaceutical sector and to public health. The proposed methodology also has great potential to accelerate screening of other therapeutics. Both the methodological and therapeutics aspects will be substantive steps to the fight against AMR. Moreover, novel therapeutics and combating AMR are fully consistent with the UN's Sustainability Development Goal (SDG) 3 in Good Health and Wellbeing. The novel methodological approaches will also strengthening Europe's scientific infrastructure and the economy.