{
  "abstract": "Mycobacterium tuberculosis (Mtb) is a major pathogen worldwide that infects and transmits only among humans, yet nearly all in vivo virulence research occurs in non-human hosts. To overcome this central challenge in tuberculosis research, we leveraged a dataset of more than 50,000 sequenced isolates to identify Mtb genes that that are functionally preserved during natural infection, disease causation, and transmission between humans. This whole-genome ranking identified polyketide synthase 12 (pks12 ) as an exceptionally in vivo essential gene in human tuberculosis, which we validated in zebrafish and mouse models. Though Pks12 produces a mycoketide lipid in only trace amounts, pks12 deletion severely altered the host-facing surface and arabinoglycan architecture of Mtb. This amplified effect was explained through the discovery of mannosyl-{beta}-1-phosphomycoketide monomycolate (MPMMM), which is synthesized from the known Pks12 product at higher abundance by antigen 85 mycolyltransferases. Thus, we used a new host-facing genomic-metabolomic-phenotypic approach to discover the functions of an in vivo essential Mtb gene, which controls the physical structure of the Mtb-host interface.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "name": "G. H. Babunovic"
    },
    {
      "name": "S. van der Niet"
    },
    {
      "name": "M. T. Gontijo"
    },
    {
      "name": "K. Abrahams"
    },
    {
      "name": "R. Sun"
    },
    {
      "name": "K. Bhatt"
    },
    {
      "name": "E. Meirav"
    },
    {
      "name": "C. Vilcheze"
    },
    {
      "name": "D. C. Young"
    },
    {
      "name": "L. Rosbach"
    },
    {
      "name": "I. Kanopaite"
    },
    {
      "name": "O. O. Adefisayo"
    },
    {
      "name": "K. M. Smith"
    },
    {
      "name": "A. M. Xet-Mull"
    },
    {
      "name": "V. G. Dellinger"
    },
    {
      "name": "E. Layre"
    },
    {
      "name": "C. M. Smith"
    },
    {
      "name": "W. R. Jacobs"
    },
    {
      "name": "A. Bhatt"
    },
    {
      "name": "G. S. Besra"
    },
    {
      "name": "D. M. Tobin"
    },
    {
      "name": "Q. Liu"
    },
    {
      "name": "N. van der Wel"
    },
    {
      "affs": [
        0
      ],
      "name": "D. B. Moody"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4k14xw5k40tss.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754250",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754250v1.full",
  "id": "4k14xw5k40tss",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754250v1",
  "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",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7214396129",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754250v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4k14xw5k40tss.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:37Z",
      "native_id": "10.64898/2026.09.25.754250",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754250v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Polyketide synthase 12 is an in vivo essential source of novel mycolyl lipids in Mycobacterium tuberculosis",
  "title_text": "Polyketide synthase 12 is an in vivo essential source of novel mycolyl lipids in Mycobacterium tuberculosis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:37Z",
  "url": "https://research.draconitic.com/paper/4k14xw5k40tss",
  "venue": "bioRxiv",
  "versions": []
}