Trypanosoma brucei Gabriela Romero-Meza1 and Monica R. Mugnier1, * 1 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA TrendsTrendsininParasitologyParasitology Trypanosoma brucei causes African trypanosomiasis in humans and nagana in domestic animals. This vectorborne parasite, transmitted by the tsetse fly, affects rural areas in sub-Saharan Africa. When injected by the fly, metacyclic-form parasites are introduced into the host dermis and then disseminate into the bloodstream as replicative long slender forms. Throughout its life cycle, T. brucei is entirely extracellular. To evade host antibody recognition, the parasite uses antigenic variation: it periodically changes a dense coat of only one kind of variant surface glycoprotein (VSG), drawing from a genomic repertoire of about 2000 VSG-encoding genes. Using quorum sensing mechanisms, slender forms develop into stumpy forms that are preadapted to the insect environment. Once taken up by the fly, the parasite replaces its VSG coat with procyclins and progresses through procyclic and epimastigote stages. Finally, the parasites become VSG-expressing metacyclic trypomastigotes. TrendsTrendsininParasitologyParasitology KEY FACTS: T. brucei possesses a unique organelle, the kinetoplast: a network of circular DNA inside a single mitochondrion. The 35 Mb diploid genome contains three types of chromosome: megabase, intermediate, and minichromosomes. The 11 megabase chromosomes contain the majority of transcriptionally active genes arranged in polycistronic units, as well as subtelomeric arrays of silent VSG genes. Minichromosomes and intermediate chromosomes contain VSG genes and DNA repeats. T. brucei typically invades tissues, including blood, lymph, bone marrow, skin, brain, eye, and heart. DISEASE FACTS: T. brucei is lysed by a primate serum component called trypanosome lytic factor (TLF), rendering it noninfectious to humans. Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are resistant to TLF and can infect humans. Symptoms in the early stage of infection: fever, joint pain, and swollen lymph nodes. In the late stage the central nervous system is affected. Detection of parasites in body fluids by microscopy is required for diagnosis. After treatment, patients are monitored for relapse by a periodic check for parasites and leukocyte counts in the cerebrospinal fluid. Affected populations live in areas with limited access to diagnosis and treatment, but human African trypanosomiasis is on its way to elimination in most endemic countries. TAXONOMY AND CLASSIFICATION: PHYLUM: Euglenozoa CLASS: Kinetoplastida ORDER: Kinetoplastida FAMILY: Trypanosomatidae GENUS: Trypanosoma SPECIES: T. brucei *Correspondence: mmugnie1@jhu.edu (M.R. Mugnier). Trends in Parasitology, June 2020, 36, No. 6 © 2019 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.pt.2019.10.007 571 Trends in Parasitology | Parasite of the Month Acknowledgments M.R.M. is supported by the Office of the Director, National Institutes of Health (DP5OD023065). VSG figure adapted from Engstler, 2007. We thank Jay Bangs, School of Medicine, University at Buffalo, and Peter Bush, School of Dental Medicine, University at Buffalo, for the T. brucei scanning electron microscope (SEM) image. Resources www.cdc.gov/parasites/sleepingsickness/ www.who.int/trypanosomiasis_african/parasite/en/ https://tritrypdb.org/tritrypdb/ Literature 1. Shapiro, T.A. et al. (1995) The structure and replication of kinetoplast DNA. Annu. Rev. Microbiol. 49, 117–143 2. Berriman, M. et al. (2005) The genome of the African trypanosome Trypanosoma brucei. Science 309, 416–422 3. Engstler, M. et al. (2007) Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131, 505–515 4. Hendriks, E. et al. (2000) Life-cycle differentiation in Trypanosoma brucei: molecules and mutants. Biochem. Soc. Trans. 28, 531–536 5. Jackson, A.P. et al. (2013) A cell-surface phylome for African Trypanosomes. PLoS Negl. Trop. Dis. 7, e2121–17 6. Matthews, K.R. (2013) Bloodstream form pre-adaptation to the tsetse fly in Trypanosoma brucei. Front. Cell Infect. Microbiol. 3, 78 7. Büscher, P. et al. (2017) Human African trypanosomiasis. Lancet 390, 2397–2409 8. Mugnier, M.R. et al. (2016) Masters of disguise: antigenic variation and the VSG coat in Trypanosoma brucei. PLoS Pathog 12 e1005784–6 9. Bangs, J.D. (2018) Evolution of antigenic variation in African Trypanosomes: variant surface glycoprotein expression, structure, and function. Bioessays 40 e1800181–8 10. Silva Pereira, S. et al. (2019) Tissue tropism in parasitic diseases. Open Biol 9, 190036 Trends in Parasitology | Parasite of the Month 572 Trends in Parasitology, June 2020, 36, No. 6 © 2019 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.pt.2019.10.007