{
  "abstract": "In the mammalian host, Trypanosoma brucei proliferates as slender bloodstream forms before undergoing quorum-sensing (QS)-dependent differentiation into non-dividing transmissible stumpy-QS forms, a process that both controls parasitaemia and enables transmission to the tsetse fly. However, this model does not explain how transmission occurs in chronically infected patients and cattle, where parasite densities are often too low to trigger QS-mediated differentiation. We identify a relevant glycerol-dependent pathway driven by adipocyte-derived glycerol that offers an explanation for this transmission paradox. We show that, at low parasite density, and with physiological levels of glycerol (0.2 mM) and glucose (4 mM) mimicking adipose and hypodermal interstitial fluids, glycerol promotes the emergence of novel proliferative forms that we termed, slender-Glyc forms. These cells are transmissible, unlike the slender forms, since they (i) differentiate in vitro into procyclic forms, which appear in the midgut of the infected flies, and (ii) establish infections in the fly. In addition, at high parasite density, tissular amounts of glycerol extends the lifespan of stumpy-QS forms (named stumpy-QS/Glyc), increasing transmission chances for tissue parasites, especially in the skin. Altogether, our findings suggest that local metabolic conditions, either on their own or in combination with parasite density, can drive transmission capacity.\n\nTrypanosoma brucei is an extracellular parasite that causes the neglected tropical disease human African trypanosomiasis (HAT), also known as sleeping sickness, and animal African trypanosomiases (AAT), such as nagana. This parasite undergoes a complex life cycle as it transits from the bloodstream of a mammalian host in bloodstream forms (BSF) to the alimentary tract in procyclic forms (PCF) and salivary glands of its blood-feeding insect vector, the tsetse fly. The extracellular fluids of the mammalian host, including blood and interstitial fluids, are rich in glucose, the main carbon source used by BSF trypanosomes to fuel their central carbon metabolism and ATP production. However, glucose can be successfully replaced by glycerol in vitro to feed the parasite's central metabolism, suggesting that this alternative carbon source may also play a role in trypanosome infection in vivo 1-3 . Indeed, recent studies showed that BSF trypanosomes",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Mohammad El Kadri"
    },
    {
      "name": "Fabien Guegan"
    },
    {
      "name": "Parul Sharma"
    },
    {
      "name": "Estefania Calvo Alvarez"
    },
    {
      "name": "Erika Pineda"
    },
    {
      "name": "Pauline Morand"
    },
    {
      "name": "Jean Marc Tsagmo Ngoune"
    },
    {
      "name": "Justine Escard"
    },
    {
      "name": "Jean-William Dupuy"
    },
    {
      "name": "Aline Rimoldi"
    },
    {
      "name": "Nicolas Plazolles"
    },
    {
      "name": "Edern Cahoreau"
    },
    {
      "name": "Marc Biran"
    },
    {
      "name": "Michael P Barrett"
    },
    {
      "name": "Luisa M Figueiredo"
    },
    {
      "name": "Brice Rotureau"
    },
    {
      "name": "Frédéric Bringaud"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/34svgbjfgnh4q.bib",
  "cited_by": 1,
  "doi": "10.1038/s41467-026-75670-w",
  "fulltext_url": null,
  "id": "34svgbjfgnh4q",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://u-bordeaux.hal.science/hal-05732490v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.mp"
    ],
    [
      "openalex",
      "2713|Trypanosoma species research and implications"
    ]
  ],
  "openalex": "W7169576549",
  "pdf_url": "https://u-bordeaux.hal.science/hal-05732490/document",
  "pmcid": null,
  "pmid": "42469243",
  "published": "2026-07-17",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/34svgbjfgnh4q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "hal-05732490",
      "source": "hal",
      "url": "https://u-bordeaux.hal.science/hal-05732490v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.mp",
      "subfield": "microbiology"
    }
  ],
  "title": "Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions",
  "title_text": "Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/34svgbjfgnh4q",
  "venue": "Nature Communications",
  "versions": []
}