{
  "abstract": "Polymyxin antibiotic resistance mediated by the mobilized colistin resistance (MCR) enzyme threatens the last-resort treatment of deadly multidrug-resistant pathogens, including Acinetobacter baumannii, and calls for urgent mitigation efforts. We used a multifaceted approach involving computational and wet-lab techniques to identify an isoindole-benzohydrazide derivative, JNAL-042, which potentiates colistin activity in an Escherichia coli MCR-resistance phenotype screening model. JNAL-042 lacked intrinsic antibiotic activity but potentiated that of polymyxin antibiotics at 12-24 mug/ml, as demonstrated by bacterial growth susceptibility screens. Cell viability counts and time-kill assays corroborated these findings, demonstrating complete abolition of MCR-mediated resistance by the antibiotic-adjuvant combination at concentrations mirroring those of empty vector controls. Post-induction treatment with this combination similarly prevented the propagation of the resistance phenotype, albeit at a higher antibiotic dose. This landmark study presents JNAL-042 as a promising antibiotic adjuvant to combat MCR-mediated resistance and offers a viable solution to preserve last-resort polymyxin antibiotics.",
  "abstract_shown": true,
  "affiliations": [
    "Miami University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "A. S. Wolf"
    },
    {
      "name": "R. O. Ndupu"
    },
    {
      "affs": [
        0
      ],
      "name": "J. N. Alumasa"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7w3c0jy84r1d0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.758198",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758198v1.full",
  "id": "7w3c0jy84r1d0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758198v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "1313|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7221523023",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758198v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7w3c0jy84r1d0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:20Z",
      "native_id": "10.64898/2026.10.10.758198",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758198v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Isoindole-benzohydrazide derivative potentiates colistin activity to overcome resistance conferred by MCR-1 variants in Escherichia coli",
  "title_text": "Isoindole-benzohydrazide derivative potentiates colistin activity to overcome resistance conferred by MCR-1 variants in Escherichia coli",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:20Z",
  "url": "https://research.draconitic.com/paper/7w3c0jy84r1d0",
  "venue": "bioRxiv",
  "versions": []
}