{
  "abstract": "It is common for bacteriophages to encode proteins that are strongly inhibitory to growth of the bacterial host, and about 10% of mycobacteriophage-encoded proteins have this property. Adephagia is a Cluster K1 mycobacteriophage and prior cloning and expression of 66 Adephagia non-structural genes identified 14 that are toxic when expressed in Mycobacterium smegmatis. One of the expressed proteins, the 70-residue gp48, is highly toxic when expressed in both M. smegmatis and Mycobacterium abscessus and acts by binding to and inactivating the function of Msmeg_1828, a mannose-1-phosphate guanylyltransferase (Mpg). Mpg is an essential enzyme for biosynthesis of GDP-mannose, a precursor of several key cell wall constituents including lipoarabinomannan and phosphatidylinositol mannosides. The crystal structure of Adephagia gp48 shows that the N-terminal 43 residues form two alpha helices that strongly promote dimer formation; the C-terminal 27 residues are disordered but are predicted to bind Fe-S clusters via cysteine and histidine residues. Adephagia gp48 inhibits Mpg guanylyltransferase activity in vitro and is predicted to interrupt Mpg dimer formation. The C-terminal metal binding activity of gp48 is not required for toxicity, and non-toxic mutants have substitutions in the N-terminal alpha helices that are involved in dimerization. The selective advantage of Mpg inactivation for the phage is unclear, but it may protect from competing phages that require GDP-mannose derived molecules for efficient infection.",
  "abstract_shown": true,
  "affiliations": [
    "University of Pittsburgh, Pittsburgh USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "M. J. Lauer"
    },
    {
      "name": "K. G. Freeman"
    },
    {
      "name": "D. Jiang"
    },
    {
      "name": "J. Maneekul"
    },
    {
      "name": "A. P. VanDemark"
    },
    {
      "affs": [
        0
      ],
      "name": "G. F. Hatfull"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f3gx49kdzjspv.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.752054",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752054v1.full",
  "id": "f3gx49kdzjspv",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752054v1",
  "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",
      "microbiology"
    ],
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ]
  ],
  "openalex": "W7213537053",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752054v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f3gx49kdzjspv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:56Z",
      "native_id": "10.64898/2026.09.16.752054",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752054v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Mycobacteriophage Adephagia gp48 inhibits essential host cell wall biosynthesis enzyme mannose-1-phosphate guanylyltransferase",
  "title_text": "Mycobacteriophage Adephagia gp48 inhibits essential host cell wall biosynthesis enzyme mannose-1-phosphate guanylyltransferase",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:56Z",
  "url": "https://research.draconitic.com/paper/f3gx49kdzjspv",
  "venue": "bioRxiv",
  "versions": []
}