{
  "abstract": "Background Targeted-Antibacterial Plasmids (TAPs) are engineered mobile genetic elements that use bacterial conjugation to deliver selective CRISPR/Cas9 antibacterial activity against a specific target strain. Yet, the efficiency of TAPs is typically evaluated at a single time point, whereas the success of TAP-mediated resensitization critically depends on the dynamics of plasmid transfer and the complex interactions between bacterial subpopulations. This is the first study to evaluate the efficiency of a conjugation-based antibacterial approach at the subpopulation level, using an analytical framework analogous to that used for conventional antibiotics. Here, we investigate which process limits resensitization by TAPF-dCas9-OXA48: plasmid delivery, dCas9 activity, or the emergence of refractory and escape populations. Methods We fitted a mechanistic model of five interacting subpopulations (donors, recipients, transconjugants, escapers, and recusants) to 44 longitudinal conjugation experiments and used the fitted model to explore a range of biologically relevant scenarios. Results Using longitudinal conjugation data spanning 24 h, we show that up to 24% of recipients become recusants within 24h, refractory to further conjugation via entry exclusion, while secondary transconjugant emergence stays below 0.01%. Overall resensitization efficiency reaches up to 80%. Conclusion Plasmid transfer, rather than dCas9 repression, therefore appears to be the main bottleneck limiting the efficiency of TAPF-dCas9-OXA48 efficiency. These results identify plasmid delivery as a key engineering target for improving the performance of future TAPs.",
  "abstract_shown": true,
  "affiliations": [
    "INSERM U1070, Universite de Poitiers, CHU de Poitiers"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "S. Marolleau"
    },
    {
      "name": "J. Moreau"
    },
    {
      "name": "J. M. Buyck"
    },
    {
      "name": "S. Bigot"
    },
    {
      "name": "C. Lesterlin"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Gregoire"
    },
    {
      "name": "V. Aranzana-Climent"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3cqz5a26sr7kt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748484",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748484v1.full",
  "id": "3cqz5a26sr7kt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748484v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7204705952",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748484v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3cqz5a26sr7kt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:27Z",
      "native_id": "10.64898/2026.09.01.748484",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748484v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Model-based evaluation of Targeted-Antibacterial-Plasmids (TAPs) transfer kinetics and resensitization of pOXA-48 carbapenem-resistant Escherichia coli",
  "title_text": "Model-based evaluation of Targeted-Antibacterial-Plasmids (TAPs) transfer kinetics and resensitization of pOXA-48 carbapenem-resistant Escherichia coli",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:27Z",
  "url": "https://research.draconitic.com/paper/3cqz5a26sr7kt",
  "venue": "bioRxiv",
  "versions": []
}