{
  "abstract": "Odilorhabdins (ODLs) are a novel class of peptide antibiotics that inhibit bacterial translation by binding to the 30S ribosomal subunit. Xenorhabdus nematophila , an ODL-producing bacterium, encodes a highly specialized self-resistance acetyltransferase, OatA, that inactivates ODLs via primary amine modification. In this study, we investigated the structural determinants governing susceptibility of the natural compound NOSO-95C to OatA-mediated inactivation. Using an alanine-scanning library, we identified N -terminal lysine (Lys 1 ) as the key structural determinant of acetyltransferase susceptibility. Expression of oatA in E. coli increased the MIC of NOSO-95C by 64-fold due to rapid OatA-mediated acetylation. In contrast, analog 1 (Lys1→Ala) was no longer discriminated between Oat-A expressing and non-expressing strains, and remained 95.4% unacetylated after 4 h of incubation. Functional assays confirmed that analog 1 retains potent translation inhibition and antibacterial activity despite enzyme exposure. Furthermore, OatA failed to inactivate other amine-containing clinical antibiotics such as aminoglycosides, penicillin, or polymyxins. These results indicate that the side chain of N -terminal lysine is essential for efficient OatA-mediated acetylation of ODLs. Moreover, this single residue can be modified to enable ODLs to evade enzymatic inactivation while preserving their primary mechanism of action. This work provides a clear structure-activity framework for the rational design of next-generation ODLs with enhanced stability against OatA-mediated enzymatic modification.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Emilie Racine"
    },
    {
      "name": "Anne Lanois-Nouri"
    },
    {
      "name": "Jessica Houard"
    },
    {
      "name": "Lucile Pantel"
    },
    {
      "name": "Alain Givaudan"
    },
    {
      "name": "Maxime Gualtieri"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bwttgbyvhzbbm.bib",
  "cited_by": 0,
  "doi": "10.1128/aac.00743-26",
  "fulltext_url": null,
  "id": "bwttgbyvhzbbm",
  "issns": [
    "0066-4804",
    "1098-6596"
  ],
  "landing_url": "https://hal.science/hal-05848235v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2404|Antimicrobial Peptides and Activities"
    ]
  ],
  "openalex": "W7213440191",
  "pdf_url": "https://hal.science/hal-05848235/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": "American Society for Microbiology",
  "ris": "https://research.draconitic.com/paper/bwttgbyvhzbbm.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:48Z",
      "native_id": "hal-05848235",
      "source": "hal",
      "url": "https://hal.science/hal-05848235v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2404|Antimicrobial Peptides and Activities",
      "subfield": "microbiology"
    }
  ],
  "title": "N-terminal lysine as a critical determinant of odilorhabdin susceptibility to inactivation by the self-resistance acetyltransferase OatA",
  "title_text": "N-terminal lysine as a critical determinant of odilorhabdin susceptibility to inactivation by the self-resistance acetyltransferase OatA",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:20:48Z",
  "url": "https://research.draconitic.com/paper/bwttgbyvhzbbm",
  "venue": "Antimicrobial Agents and Chemotherapy",
  "versions": []
}