Kinetoplastid Drug Development: strengthening the preclinical pipeline

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Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice

Publication . Trindade, Sandra; Rijo-Ferreira, Filipa; Carvalho, Tânia; Neves, Daniel; Guegan, Fabien Marc; Aresta-Branco, Francisco; Bento, Fabio; Young, Simon A.; Pinto, Andreia; Van Den Abbeele, Jan; Ribeiro, Ruy M.; Dias, Sérgio; Smith, Terry K.; Figueiredo, Luisa M.

Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenous myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. These findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.

2016Journal article

Open access