Parasite Physiology: Trypanosomes Chew The

RESEARCH HIGHLIGHTS

Nature Reviews Microbiology | Published online 31 May 2016; doi:10.1038/nrmicro.2016.86

PARASITE PHYSIOLOGY Trypanosomes chew the fat

Trypanosoma brucei is an extracellular adipose tissue is a novel niche that protozoan parasite that is the causative is occupied by T. brucei during the agent of human African trypanoso- infection of mammalian hosts. miasis, a frequently fatal disease that In the early stages of mammalian is commonly known as sleeping sick- infection, T. brucei adopts a mor- ness. The life cycle of T. brucei involves phologically ‘slender’ form, which is infection of the vector, the tsetse fly, replicative, whereas during the later and transmission to the blood of stages of infection slender parasites mammalian hosts through the bite of can differentiate into a morpho- the fly. Two major niches have been logically ‘stumpy’ form, which is described for T. brucei in mammalian growth-arrested. Using a fluorescent hosts: the blood and, after crossing marker of a developmental gene, the the blood–brain barrier, the central authors tracked the distribution of nervous system. However, Trindade developmental stages of the parasite et al. now show that adipose tissue in the mouse model. At 4 days Trypanosoma brucei. Image courtesy of T. Carvalho and A. L. Pinto, Universidade de Lisboa, Portugal. is a third major niche for T. brucei in post-infection, 98% of parasites in the mammalian hosts and, furthermore, blood remained in the slender form, that the parasite may use the fatty whereas at 6 days post-infection, 86% in adipose tissue, notably fatty acids. acids that are present in this tissue as a of parasites in the blood were differen- Indeed, of particular interest was the carbon source. tiated into the stumpy form or, more upregulation of genes with functions Immunohistochemistry of mice rarely, a developmentally intermediate in the β-oxidation of fatty acids, as that were infected with T. brucei form. Adipose tissue also contained a this metabolic pathway is not active in showed that, in addition to blood, mixed population of these three devel- T. brucei in other niches. Pulse–chase parasites are present in the interstitial opmental stages, as was confirmed by experiments using radiolabelled space of several organs, including morphological examination. However, myristate as a fatty acid confirmed adipose tissue. A quantitative only 21% of parasites in adipose tissue that the fatty acid β-oxidation comparison, based on the amount of were differentiated into stumpy or pathway was active in parasites from parasite DNA, showed that the para- intermediate forms at 6 days post- adipose tissue but not from blood. adipose tissue site density in adipose tissue was only infection. Cell-cycle analysis and the Prompted by this finding, the authors is a novel seven-times lower than in blood at injection of adipose tissue into naive note that an aetiologically unex- niche that 6 days post-infection, and sixty-times mice demonstrated that parasites in plained symptom of sleeping sickness higher than in other organs. The adipose tissue remain competent for is weight loss, and speculate that the is occupied parasite density in blood decreased replication and infection. metabolism of fatty acids by parasites by T. brucei during the course of infection; how- Finally, comparative analysis of in adipose tissue might contribute to during the ever, the parasite density in adipose the transcriptomes of parasites in the weight loss in infected individuals. infection of tissue remained constant, such that by blood and parasites in adipose tissue Naomi Attar 28 days post-infection adipose tissue revealed the differential expression of mammalian ORIGINAL ARTICLE Trindade, S. et al. was the site of highest parasite density, many genes with functions in meta- Trypanosoma brucei parasites occupy and hosts which corresponded to a total parasite bolic pathways, which suggests that functionally adapt to the adipose tissue in mice. load that was higher in adipose tissue T. brucei may adapt its metabolism Cell Host Microbe http://dx.doi.org/10.1016/j. chom.2016.05.002 (2016) than in all other sites combined. Thus, to the energy sources that are present