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

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. Lastly, 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.
Authors:
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [3] ;  [1] ;  [4] ; ORCiD logo [5] ;  [1] ;  [3] ;  [1]
  1. Univ. de Lisboa, Lisboa (Portugal)
  2. Univ. de Lisboa, Lisboa (Portugal); Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Univ. do Porto, Porto (Portugal)
  3. Univ. of St. Andrews, Fife (United Kingdom)
  4. Institute of Tropical Medicine Antwerp, Antwerp (Belgium); Univ. of Ghent, Ghent (Belgium)
  5. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. de Lisboa, Lisboa (Portugal)
Publication Date:
Report Number(s):
LA-UR-16-23520
Journal ID: ISSN 1931-3128
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 19; Journal Issue: 6; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
National Institutes of Health (NIH); USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biological science; African trypanosomes; fat; mouse infection; fatty acid β-oxidation; metabolism; transcriptome
OSTI Identifier:
1341864