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

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

doi:10.1016/j.chom.2016.05.002

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

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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	837-848
Number of pages	13
Journal	Cell Host & Microbe
Volume	19
Issue number	6
Early online date	26 May 2016
DOIs	https://doi.org/10.1016/j.chom.2016.05.002
Publication status	Published - 8 Jun 2016

Keywords

African trypanosomes
Fat
Mouse infection
Fatty acid β-oxidation
Metabolism
Transcriptome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.chom.2016.05.002Licence: CC BY

Smith_2016_CH&M_AdiposeTissue_CC
Copyright © 2016 The Author(s). Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Final published version, 4.64 MBLicence: CC BY

lipid catabolism: Investigating the typanosomatid lysosome and its role in lipid catabolism.
Smith, T. K. (PI)
Medical Research Council
1/06/15 → 31/01/19
Project: Standard
EU KINDRED: EU KINDRED-Management
Smith, T. K. (PI)
European Commission
1/09/13 → 31/08/16
Project: Standard
Investigating Trypanosoma brucei's: Investigating Trypanosoma Brucei's Unusual Inositol Metabolism
Smith, T. K. (PI)
The Wellcome Trust
1/01/11 → 31/03/14
Project: Standard

Terry K Smith
- tks1st-andrews.acuk
- School of Biology - Director of Biomedical Sciences Research Complex, Professor
- Sir James Mackenzie Institute for Early Diagnosis
- Biomedical Sciences Research Complex
Person: Academic

Cite this

Trindade, S., Rijo-Ferreira, F., Carvalho, T., Pinto-Neves, D., Guegan, F., Aresta-Branco, F., Bento, F., Young, S. A., Pinto, A., Van Den Abbeele, J., Ribeiro, RM., Dias, S., Smith, T. K., & Figueiredo, LM. (2016). Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell Host & Microbe, 19(6), 837-848. https://doi.org/10.1016/j.chom.2016.05.002

@article{a019b7ccdbdd41e1819f05de8aa678ce,

title = "Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice",

abstract = "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.",

keywords = "African trypanosomes, Fat, Mouse infection, Fatty acid β-oxidation, Metabolism, Transcriptome",

author = "Sandra Trindade and Filipa Rijo-Ferreira and T{\^a}nia Carvalho and Daniel Pinto-Neves and Fabien Guegan and Francisco Aresta-Branco and Fabio Bento and Young, {Simon A.} and Andreia Pinto and Jan Van Den Abbeele and Ruy M. Ribeiro and S{\'e}rgio Dias and Smith, {Terry K} and Luisa M. Figueiredo",

note = "This work was supported by 55007419 (HHMI) and 2151 (EMBO) to L.M.F., D.P.-N., F.B., and F.G.; FCT fellowships to S.T., F.R.-F., and F.A.-B. (SFRH/BPD/89833/2012, SFRH/BD/51286/2010, and SFRH/BD/80718/2011, respectively); Wellcome Trust grant (093228), MRC MR/M020118/1, and European Community Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED) to S.A.Y. and T.K.S.; and PAI 7/41 (Belspo) and ERC-NANOSYM to J.V.D.A.",

year = "2016",

month = jun,

day = "8",

doi = "10.1016/j.chom.2016.05.002",

language = "English",

volume = "19",

pages = "837--848",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "6",

}

Trindade, S, Rijo-Ferreira, F, Carvalho, T, Pinto-Neves, D, Guegan, F, Aresta-Branco, F, Bento, F, Young, SA, Pinto, A, Van Den Abbeele, J, Ribeiro, RM, Dias, S, Smith, TK & Figueiredo, LM 2016, 'Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice', Cell Host & Microbe, vol. 19, no. 6, pp. 837-848. https://doi.org/10.1016/j.chom.2016.05.002

TY - JOUR

T1 - Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice

AU - Trindade, Sandra

AU - Rijo-Ferreira, Filipa

AU - Carvalho, Tânia

AU - Pinto-Neves, Daniel

AU - Guegan, Fabien

AU - Aresta-Branco, Francisco

AU - Bento, Fabio

AU - Young, Simon A.

AU - Pinto, Andreia

AU - Van Den Abbeele, Jan

AU - Ribeiro, Ruy M.

AU - Dias, Sérgio

AU - Smith, Terry K

AU - Figueiredo, Luisa M.

N1 - This work was supported by 55007419 (HHMI) and 2151 (EMBO) to L.M.F., D.P.-N., F.B., and F.G.; FCT fellowships to S.T., F.R.-F., and F.A.-B. (SFRH/BPD/89833/2012, SFRH/BD/51286/2010, and SFRH/BD/80718/2011, respectively); Wellcome Trust grant (093228), MRC MR/M020118/1, and European Community Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED) to S.A.Y. and T.K.S.; and PAI 7/41 (Belspo) and ERC-NANOSYM to J.V.D.A.

PY - 2016/6/8

Y1 - 2016/6/8

N2 - 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.

AB - 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.

KW - African trypanosomes

KW - Fat

KW - Mouse infection

KW - Fatty acid β-oxidation

KW - Metabolism

KW - Transcriptome

U2 - 10.1016/j.chom.2016.05.002

DO - 10.1016/j.chom.2016.05.002

M3 - Article

SN - 1931-3128

VL - 19

SP - 837

EP - 848

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Projects

lipid catabolism: Investigating the typanosomatid lysosome and its role in lipid catabolism.

EU KINDRED: EU KINDRED-Management

Investigating Trypanosoma brucei's: Investigating Trypanosoma Brucei's Unusual Inositol Metabolism

Profiles

Terry K Smith

Cite this