{
  "abstract": "Objectives People with Cystic Fibrosis (pwCF) often develop persistent lung infections caused by Pseudomonas aeruginosa (Pa) that are hard to treat. Creating new antibiotics faces several obstacles; difficult, costly and time-consuming. Thus, finding new uses for approved medications is a priority, as highlighted by the LifeArc Translational Challenge programme. Glatiramer acetate (GA), currently used to treat multiple sclerosis, is similar in structure to antimicrobial peptides such as LL-37. Our research showed enhanced killing of Pa when combining GA with tobramycin (TOB).1 This study aims to investigate the GA-TOB impact on other CF pathogens, with this portion of the study looking at GA’s effect on membrane integrity of clinical strains of Pa as well as other CF-relevant pathogens.Methods We assessed depolarisation of the cytoplasmic membrane via the release of the fluorescent dye, DiSC3(5), on a panel of CF relevant bacterial pathogens. We compared these profiles to the antimicrobial peptide LL-37, and antibiotics TOB and colistin.Results We have shown that the enhanced killing of Pa reference and clinical strains when co-treated with GA (50 µg/ml) and TOB is mediated by membrane disruption. Here we show that GA is shown to have an effect on the depolarisation of cytoplasmic membrane of Pa, Gram-negative bacteria and the Gram-positive bacteria, Staphylococcus aureus. GA also depolarised the cytoplasmic membrane across the panel of 9 species including Acinetobacter baylyi, A. baumannii, and Pseudomonas protogens. Preliminary data shows that all three of the Pa clinical isolates tested achieved membrane depolarisation with GA.Conclusions GA depolarised the cytoplasmic membranes of clinically relevant CF pathogens as well as reference strains and clinical isolates of Pa.The ability of GA to disturb the membrane of other clinically relevant CF pathogens in addition to Pa suggests it will act similarly as an antibiotic resistance breaker, by allowing increased intracellular access of antimicrobials such as TOB, expanding the potential of GA to combat bacterial airway infections.Reference Murphy RA, et al. Microbiol Spectr. 2022;10(4):e0081322.",
  "authors": [
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "A Daly-Gourdialsing"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "S Gilles"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "RF Rollo"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "ACL Micallef"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "M Zhao"
    },
    {
      "affiliations": [
        "Freie Universität Berlin, Berlin, Germany"
      ],
      "name": "RA Murphy"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK",
        "Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK"
      ],
      "name": "DA Hughes"
    },
    {
      "affiliations": [
        "Department of Biomedicine, Aarhus University, Aarhus, Denmark"
      ],
      "name": "T Vorup-Jensen"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK"
      ],
      "name": "LP Allsopp"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, UK",
        "Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK"
      ],
      "name": "JC Davies"
    }
  ],
  "title": "P183 Enhancing antibiotic effectiveness using the repurposed multiple sclerosis drug, glatiramer acetate, to compromise membrane integrity of CF-relevant pathogenic bacteria",
  "uid": "89640c6a-d251-5979-96d6-78517d4a3095"
}