{
  "abstract": "Antivirulence therapeutics are a promising strategy to combat rising antimicrobial resistance. Transcription factor proteins have shown merit as antivirulence drug targets, as demonstrated by the small molecule Savirin. Regacin was identified as a potent inhibitor of the AraC-family virulence regulator (AraC-VR) RegA of Citrobacter rodentium, providing proof-of-concept for targeting AraC-VR family members in related human enteric pathogens. The structural basis of RegA inhibition by regacin was previously undefined and could prove essential for future drug design campaigns targeting AraC-VR family members. This work reveals that RegA is structurally similar to its homologs ToxT and Rns, including a conserved ligand-binding pocket in the N-terminal domain. A regacin-RegA co-crystal structure shows regacin binds within this pocket, with some heterogeneity in binding pose. Finally, structure-guided mutagenesis of key pocket residues, validated using a {beta}-galactosidase reporter assay, confirmed their role in regacin-mediated inhibition. Together, these findings define the regacin binding site, suggest a molecular basis of RegA inhibition, and provide a framework for future inhibitor design targeting this conserved pocket in other virulence regulators in human enteric pathogens.",
  "abstract_shown": true,
  "affiliations": [
    "Dartmouth College"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "C. M. Bollinger"
    },
    {
      "affs": [
        0
      ],
      "name": "C. R. Midgett"
    },
    {
      "name": "K. M. Talbot"
    },
    {
      "name": "G. V. Lawhern"
    },
    {
      "name": "G. Munson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dy2pze8cypjtq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.11.750636",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750636v1.full",
  "id": "dy2pze8cypjtq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750636v1",
  "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",
      "microbiology"
    ],
    [
      "openalex",
      "1310|Escherichia coli research studies"
    ]
  ],
  "openalex": "W7212457326",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750636v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dy2pze8cypjtq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:47Z",
      "native_id": "10.64898/2026.09.11.750636",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750636v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "The small molecule regacin binds a conserved pocket in RegA to inhibit the expression of bacterial virulence factors",
  "title_text": "The small molecule regacin binds a conserved pocket in RegA to inhibit the expression of bacterial virulence factors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:17Z",
  "url": "https://research.draconitic.com/paper/dy2pze8cypjtq",
  "venue": "bioRxiv",
  "versions": []
}