MP: AMUT – a new anti-bacterial drug candidate with a potential to reduce antibiotic resistance development

Prof. Marit Otterlei and co-workers at NTNU discovered a new antibiotic drug candidate, a synthetic cell-penetrating peptide showing anti-bacterial activity and importantly attacking bacteria in a fundamentally new way. Several multidrug resistant (MDR) bacteria on the WHO ESKAPE list are very sensitive to this peptide, even when they grow in biofilms as they do in the majority of infections. Apart from being directly bactericidal (i.e. killing the bacteria), the drug candidate also remarkably sensitises bacteria towards other antibiotics. The peptide binds to a critical protein in the bacterial replication called beta-clamp and interferes with DNA replication and mutagenesis. This is especially important during stress responses such as those brought about by antibiotic treatment. Under stress condition, bacteria utilize error-prone processes that lead to resistance-conferring mutations and thereby antimicrobial resistance development. The basic research behind this drug candidate was recently published in the high impact journal Nucleic Acids Research (Nedal et al, 2020, Nucleic Acids Research, 48(10)). In this project we carried out a pilot study to investigate the effect of the peptide in a lung infection mice model. We used Streptococcus pneumonia model and the peptide was administered intravenously to mimic the clinical situation at pneumonia. The results are very promising and show that 3x intravenous injections of the peptide was able to reduce the bacterial load ~2log. As this was only a pilot study, we will follow-up with a larger study where we will optimize the dose and administration schemes. We will also address other indications beyond pneumonia.

Antibiotikaresistente bakterier er en global trussel som tar mange liv. Mens utvikling av antibiotikaresistens er alarmerende, har utviklingen av nye effektive antibiotika ikke fulgt med utvikling av resistens. Uten hastetiltak som vil akselerere utviklingen av nye innovative antibiotika som er i stand til å bekjempe resistente bakterier på nye måter vil antibiotikaresistens føre til alvorlige folkehelseproblemer og dramatisk innvirkning på pasientbehandlingen i fremtiden. Den nye antibiotikakandidat under utvikling på NTNU viser lovende effekt på flere multiresistente (MDR) bakterier på WHO ESKAPE-listen, har en ny virkningsmekanisme og kan dermed bli et nytt antibiotikum som kan redde liv.