{
  "abstract": "Lectin-like protein antibiotics (Llps) kill Pseudomonas by inhibiting BamA, the essential core of the beta-barrel assembly machinery (BAM). Llps are composed of one or two beta;-lectin domains and a C-terminal peptide, with characterisation to date centred on the two-domain L-type pyocins of P. aeruginosa, which bind BamA extracellular loop 6 and inhibit by delivering the C-terminal peptide to BamA beta;-strand 1. Whether this mechanism is general, and how Llps contend with BamA sequence differences across species, remained unknown. We screened 238 Pseudomonas Llps against 101 genome-sequenced isolates, showing susceptibility across the family is set by BamA extracellular loop 6. Loop 6 length varies, and Llps fall into three targeting modes: short-loop and long-loop specialists and broad-range dual targeters, which have arisen repeatedly. We determine the 2.66 angstrom cryo-electron microscopy structure of a two-domain LlpA bound to BAM, showing recognition has been relocated relative to the L-type pyocins, with loop 6 bound by a single face of the N-terminal beta-lectin domain rather than the inter-domain cleft. This explains how single-domain LlpBs retain BamA targeting and why the second lectin domain has been lost at least twice. We show that the BamA inhibition mechanism is shared across Llps, with a hypervariable C-terminal peptide binding BamA beta-strand 1, inhibiting the BAM insertase by mimicking the beta-signal of BamA substrates. Together, these data provide an atlas of Llp diversity and the mechanistic principles for engineering it, identifying Llps as a tuneable, multi-interface scaffold for BAM-directed precision antibacterials against pathogenic Pseudomonas, including economically important plant pathogens.",
  "abstract_shown": true,
  "affiliations": [
    "Monash University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "F. Munder"
    },
    {
      "name": "C. Wang"
    },
    {
      "name": "L. Jimenez"
    },
    {
      "name": "M. T. Doyle"
    },
    {
      "name": "J. P. Connolly"
    },
    {
      "name": "G. J. Knott"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Grinter"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1v7tjmt0w1tw1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754295",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754295v1.full",
  "id": "1v7tjmt0w1tw1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754295v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "2404|Antimicrobial Peptides and Activities"
    ]
  ],
  "openalex": "W7214612539",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754295v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1v7tjmt0w1tw1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:48Z",
      "native_id": "10.64898/2026.09.25.754295",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754295v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2404|Antimicrobial Peptides and Activities",
      "subfield": "microbiology"
    }
  ],
  "title": "A diverse family of protein antibiotics inhibits the BAM complex by β-signal mimicry",
  "title_text": "A diverse family of protein antibiotics inhibits the BAM complex by β-signal mimicry",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:48Z",
  "url": "https://research.draconitic.com/paper/1v7tjmt0w1tw1",
  "venue": "bioRxiv",
  "versions": []
}