Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions

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.

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Publication Details

Journal
Nature Communications
Published
2026-07-17
DOI
https://doi.org/10.1038/s41467-026-75670-w
Primary Topic
Trypanosoma species research and implications
Type
article
Field-Weighted Citation Impact
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article

Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions

Jean Marc Tsagmo, Estefanía Calvo Álvarez, Edern Cahoreau, Pauline Morand et al.
Nature Communications
Trypanosoma species research and implications
article

Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions

Jean Marc Tsagmo, Estefanía Calvo Álvarez, Edern Cahoreau, Pauline Morand, Fabien Guegan, Brice Rotureau, Jean‐William Dupuy, Erika Pineda, Nicolas Plazolles, Frédéric Bringaud, Marc Biran, Parul Sharma, Mohammad El Kadri, Luisa M. Figueiredo, Justine Escard, Michael P. Barrett, Aline Rimoldi
article en

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.

Nature Communications
Centre National de la Recherche Scientifique (FR), Université de Bordeaux (FR), Inserm (FR), Institut Pasteur (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Institut National des Sciences Appliquées de Toulouse (FR), Université Paris Cité (FR), Sorbonne Université (FR), Wellcome Centre for Molecular Parasitology (GB), Centre de Résonance Magnétique des Systèmes Biologiques (FR), Bordeaux Population Health (FR), Institut de Génomique Fonctionnelle (FR), Institut Polytechnique de Bordeaux (FR), Institut de Recherche Agronomique de Guinée (GN), Laboratoire de Microbiologie Fondamentale et Pathogénicité (FR), Instituto Gulbenkian de Ciência (PT), University of Glasgow (GB)
Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique
Openalex Percentile: Top 8%
Trypanosoma species research and implications
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