Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Basic Biology of Trypanosoma brucei with Reference to the Development of Chemotherapies

Author(s): Samuel Dean*

Volume 27, Issue 14, 2021

Published on: 19 January, 2021

Page: [1650 - 1670] Pages: 21

DOI: 10.2174/1381612827666210119105008

Price: $65

Abstract

Trypanosoma brucei are protozoan parasites that cause the lethal human disease African sleeping sickness and the economically devastating disease of cattle, Nagana. African sleeping sickness, also known as Human African Trypanosomiasis (HAT), threatens 65 million people and animal trypanosomiasis makes large areas of farmland unusable. There is no vaccine and licensed therapies against the most severe, late-stage disease are toxic, impractical and ineffective. Trypanosomes are transmitted by tsetse flies, and HAT is therefore predominantly confined to the tsetse fly belt in sub-Saharan Africa. They are exclusively extracellular and they differentiate between at least seven developmental forms that are highly adapted to host and vector niches. In the mammalian (human) host they inhabit the blood, cerebrospinal fluid (late-stage disease), skin, and adipose fat. In the tsetse fly vector they travel from the tsetse midgut to the salivary glands via the ectoperitrophic space and proventriculus. Trypanosomes are evolutionarily divergent compared with most branches of eukaryotic life. Perhaps most famous for their extraordinary mechanisms of monoallelic gene expression and antigenic variation, they have also been investigated because much of their biology is either highly unconventional or extreme. Moreover, in addition to their importance as pathogens, many researchers have been attracted to the field because trypanosomes have some of the most advanced molecular genetic tools and database resources of any model system. The following will cover just some aspects of trypanosome biology and how its divergent biochemistry has been leveraged to develop drugs to treat African sleeping sickness. This is by no means intended to be a comprehensive survey of trypanosome features. Rather, I hope to present trypanosomes as one of the most fascinating and tractable systems to do discovery biology.

Keywords: Trypanosoma brucei, trypanosome, kinetoplastid, parasite, African sleeping sickness, trypanosomiasis, chemotherapy, cell biology, life cycle, tsetse fly.

[1]
Lukeš J, Skalický T, Týč J, Votýpka J, Yurchenko V. Evolution of parasitism in kinetoplastid flagellates. Mol Biochem Parasitol 2014; 195(2): 115-22.
[http://dx.doi.org/10.1016/j.molbiopara.2014.05.007] [PMID: 24893339]
[2]
Simpson AGB, Stevens JR, Lukeš J. The evolution and diversity of kinetoplastid flagellates. Trends Parasitol 2006; 22(4): 168-74.
[http://dx.doi.org/10.1016/j.pt.2006.02.006] [PMID: 16504583]
[3]
Flegontov P, Votýpka J, Skalický T, et al. Paratrypanosoma is a novel early-branching trypanosomatid. Curr Biol 2013; 23(18): 1787-93.
[http://dx.doi.org/10.1016/j.cub.2013.07.045] [PMID: 24012313]
[4]
Dyková I, Fiala I, Lom J, Lukeš J. Perkinsiella amoebae-like endosymbionts of Neoparamoeba spp., relatives of the kinetoplastid Ichthyobodo. Eur J Protistol 2003; 39(1): 37-52.
[http://dx.doi.org/10.1078/0932-4739-00901]
[5]
Tanifuji G, Cenci U, Moog D, et al. Genome sequencing reveals metabolic and cellular interdependence in an amoeba-kinetoplastid symbiosis. Sci Rep 2017; 7(1): 11688.
[http://dx.doi.org/10.1038/s41598-017-11866-x] [PMID: 28916813]
[6]
Steverding D. The history of African trypanosomiasis. Parasit Vectors 2008; 1(1): 3.
[http://dx.doi.org/10.1186/1756-3305-1-3] [PMID: 18275594]
[7]
Croft AM, Kitson MM, Jackson CJ, Minton EJ, Friend HM. African trypanosomiasis in a British soldier. Mil Med 2007; 172(7): 765-9.
[http://dx.doi.org/10.7205/MILMED.172.7.765] [PMID: 17691692]
[8]
Kennedy PG. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol 2013; 12(2): 186-94.
[http://dx.doi.org/10.1016/S1474-4422(12)70296-X] [PMID: 23260189]
[9]
Wengert O, Kopp M, Siebert E, et al. Human African trypanosomiasis with 7-year incubation period: clinical, laboratory and neuroimaging findings. Parasitol Int 2014; 63(3): 557-60.
[http://dx.doi.org/10.1016/j.parint.2014.02.003] [PMID: 24613272]
[10]
Sudarshi D, Lawrence S, Pickrell WO, Eligar V, Walters R, Quaderi S, et al. Human African Trypanosomiasis Presenting at Least 29 Years after Infection-What Can This Teach Us about the Pathogenesis and Control of This Neglected Tropical Disease? Franco-Paredes C, editor PLoS Negl Trop Dis. 2014; 8: p. (12)e3349..
[11]
Capewell P, Atkins K, Weir W, et al. Resolving the apparent transmission paradox of African sleeping sickness. PLoS Biol 2019; 17(1), e3000105.
[http://dx.doi.org/10.1371/journal.pbio.3000105] [PMID: 30633739]
[12]
Mehlitz D, Molyneux DH. The elimination of Trypanosoma brucei gambiense? Challenges of reservoir hosts and transmission cycles: Expect the unexpected. Parasite Epidemiol Control 2019; 6, e00113.
[http://dx.doi.org/10.1016/j.parepi.2019.e00113] [PMID: 31528738]
[13]
Ebhodaghe F, Isaac C, Ohiolei JA. A meta-analysis of the prevalence of bovine trypanosomiasis in some African countries from 2000 to 2018. Prev Vet Med 2018; 160: 35-46.
[http://dx.doi.org/10.1016/j.prevetmed.2018.09.018] [PMID: 30388996]
[14]
Bruce D. The morphology of Trypanosoma gambiense (Dutton). Proc R Soc Lond, B 1911; 84(572): 327-32.
[http://dx.doi.org/10.1098/rspb.1911.0079]
[15]
Bruce D, Harvey D, Hamerton AE, Davey JB. Bruce, Lady. The morphology of the trypanosome causing disease in man in Nyasaland. Proc R Soc Lond, B 1912; 85(581): 423-33.
[http://dx.doi.org/10.1098/rspb.1912.0068]
[16]
Bargul JL, Jung J, McOdimba FA, et al. Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host. PLoS Pathog 2016; 12(2), e1005448.
[http://dx.doi.org/10.1371/journal.ppat.1005448] [PMID: 26871910]
[17]
Vickerman K, Tetley L, Hendry KAK, Turner CMR. Biology of African trypanosomes in the tsetse fly. Biol Cell 1988; 64(2): 109-19.
[http://dx.doi.org/10.1016/0248-4900(88)90070-6] [PMID: 3067793]
[18]
Schuster S, Krüger T, Subota I, Thusek S, Rotureau B, Beilhack A, et al. Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifacetedin vivo microswimmer system.Soldati-Favre D, editor eLife. 2017; 6: p. e27656..
[19]
Wheeler RJ. Use of chiral cell shape to ensure highly directional swimming in trypanosomes. PLOS Comput Biol 2017; 13(1), e1005353.
[http://dx.doi.org/10.1371/journal.pcbi.1005353] [PMID: 28141804]
[20]
Matthews KR, Gull K. Evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of African trypanosomes. J Cell Biol 1994; 125(5): 1147-56.
[http://dx.doi.org/10.1083/jcb.125.5.1147] [PMID: 8195296]
[21]
Reuner B, Vassella E, Yutzy B, Boshart M. Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture. Mol Biochem Parasitol 1997; 90(1): 269-80.
[http://dx.doi.org/10.1016/S0166-6851(97)00160-6] [PMID: 9497048]
[22]
Vassella E, Reuner B, Yutzy B, Boshart M. Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway. J Cell Sci 1997; 110(Pt 21): 2661-71.
[PMID: 9427384]
[23]
Mony BM, MacGregor P, Ivens A, et al. Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei. Nature 2014; 505(7485): 681-5.
[http://dx.doi.org/10.1038/nature12864] [PMID: 24336212]
[24]
Rojas F, Silvester E, Young J, et al. Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing. Cell 2019; 176(1-2): 306-317.e16.
[http://dx.doi.org/10.1016/j.cell.2018.10.041] [PMID: 30503212]
[25]
Silvester E, Young J, Ivens A, Matthews KR. Interspecies quorum sensing in co-infections can manipulate trypanosome transmission potential. Nat Microbiol 2017; 2(11): 1471-9.
[http://dx.doi.org/10.1038/s41564-017-0014-5] [PMID: 28871083]
[26]
Robertson M. Notes on the polymorphism of Trypanosoma gambiense in the blood and its relation to the exogenous cycle in Glossina palpalis. Proc R Soc Lond, B 1912; 85(582): 527-39.
[http://dx.doi.org/10.1098/rspb.1912.0080]
[27]
Tasker M, Wilson J, Sarkar M, Hendriks E, Matthews K. A novel selection regime for differentiation defects demonstrates an essential role for the stumpy form in the life cycle of the African trypanosome. Mol Biol Cell 2000; 11(5): 1905-17.
[http://dx.doi.org/10.1091/mbc.11.5.1905] [PMID: 10793160]
[28]
Vickerman K. Developmental cycles and biology of pathogenic trypanosomes. Br Med Bull 1985; 41(2): 105-14.
[http://dx.doi.org/10.1093/oxfordjournals.bmb.a072036] [PMID: 3928017]
[29]
Polymorphism VK, Mitochondrial AISST. Nature 1965; 208(5012): 762-6.
[http://dx.doi.org/10.1038/208762a0] [PMID: 5868887]
[30]
Wijers DJB, Willett KC. Factors that may influence the infection rate of Glossina palpalis with Trypanosoma gambiense. II. The number and morphology of the trypano-somes present in the blood of the host at the time of the infected feed. Ann Trop Med Parasitol 1960; 54(3): 341-50.
[http://dx.doi.org/10.1080/00034983.1960.11685996] [PMID: 13785187]
[31]
Ziegelbauer K, Quinten M, Schwarz H, Pearson TW, Overath P. Synchronous differentiation of Trypanosoma brucei from bloodstream to procyclic formsin vitro. Eur J Biochem 1990; 192(2): 373-8.
[http://dx.doi.org/10.1111/j.1432-1033.1990.tb19237.x] [PMID: 1698624]
[32]
Dean S, Marchetti R, Kirk K, Matthews KR. A surface transporter family conveys the trypanosome differentiation signal. Nature 2009; 459(7244): 213-7.
[http://dx.doi.org/10.1038/nature07997] [PMID: 19444208]
[33]
Engstler M, Boshart M. Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in Trypanosoma brucei. Genes Dev 2004; 18(22): 2798-811.
[http://dx.doi.org/10.1101/gad.323404] [PMID: 15545633]
[34]
Nolan DP, Rolin S, Rodriguez JR, Van Den Abbeele J, Pays E. Slender and stumpy bloodstream forms of Trypanosoma brucei display a differential response to extracellular acidic and proteolytic stress. Eur J Biochem 2000; 267(1): 18-27.
[http://dx.doi.org/10.1046/j.1432-1327.2000.00935.x] [PMID: 10601846]
[35]
Rolin S, Hancocq-Quertier J, Paturiaux-Hanocq F, Nolan DP, Pays E. Mild acid stress as a differentiation trigger in Trypanosoma brucei. Mol Biochem Parasitol 1998; 93(2): 251-62.
[http://dx.doi.org/10.1016/S0166-6851(98)00046-2] [PMID: 9662709]
[36]
Caljon G, Van Reet N, De Trez C, Vermeersch M, Pérez-Morga D, Van Den Abbeele J. The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies. PLoS Pathog 2016; 12(7), e1005744.
[http://dx.doi.org/10.1371/journal.ppat.1005744] [PMID: 27441553]
[37]
Capewell P, Cren-Travaillé C, Marchesi F, et al. The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes. eLife 2016; 5, e17716.
[http://dx.doi.org/10.7554/eLife.17716] [PMID: 27653219]
[38]
Trindade S, Rijo-Ferreira F, Carvalho T, et al. Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice. Cell Host Microbe 2016; 19(6): 837-48.
[http://dx.doi.org/10.1016/j.chom.2016.05.002] [PMID: 27237364]
[39]
Vickerman K. On the surface coat and flagellar adhesion in trypanosomes. J Cell Sci 1969; 5(1): 163-93.
[PMID: 5353653]
[40]
Ferrante A, Allison AC. Alternative pathway activation of complement by African trypanosomes lacking a glycoprotein coat. Parasite Immunol 1983; 5(5): 491-8.
[http://dx.doi.org/10.1111/j.1365-3024.1983.tb00763.x] [PMID: 6634218]
[41]
McLintock LML, Turner CMR, Vickerman K. Comparison of the effects of immune killing mechanisms on Trypanosoma brucei parasites of slender and stumpy morphology. Parasite Immunol 1993; 15(8): 475-80.
[http://dx.doi.org/10.1111/j.1365-3024.1993.tb00633.x] [PMID: 8233562]
[42]
Engstler M, Thilo L, Weise F, et al. Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei. J Cell Sci 2004; 117(Pt 7): 1105-15.
[http://dx.doi.org/10.1242/jcs.00938] [PMID: 14996937]
[43]
Overath P, Engstler M. Endocytosis, membrane recycling and sorting of GPI-anchored proteins: Trypanosoma brucei as a model system. Mol Microbiol 2004; 53(3): 735-44.
[http://dx.doi.org/10.1111/j.1365-2958.2004.04224.x] [PMID: 15255888]
[44]
Dean SD, Matthews KR. Restless gossamers: antibody clearance by hydrodynamic flow forces generated at the surface of motile trypanosome parasites. Cell Host Microbe 2007; 2(5): 279-81.
[http://dx.doi.org/10.1016/j.chom.2007.10.006] [PMID: 18005745]
[45]
Engstler M, Pfohl T, Herminghaus S, et al. Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 2007; 131(3): 505-15.
[http://dx.doi.org/10.1016/j.cell.2007.08.046] [PMID: 17981118]
[46]
Cheung JLY, Wand NV, Ooi C-P, Ridewood S, Wheeler RJ, Rudenko G. Blocking Synthesis of the Variant Surface Glycoprotein Coat in Trypanosoma brucei Leads to an Increase in Macrophage Phagocytosis Due to Reduced Clearance of Surface Coat Antibodies. PLoS Pathog 2016; 12(11), e1006023.
[http://dx.doi.org/10.1371/journal.ppat.1006023] [PMID: 27893860]
[47]
Ooi C-P, Rudenko G. How to create coats for all seasons: elucidating antigenic variation in African trypanosomes. Emerg Top Life Sci 2017; 1(6): 593-600.
[http://dx.doi.org/10.1042/ETLS20170105]
[48]
Cross GAM, Kim H-S, Wickstead B. Capturing the variant surface glycoprotein repertoire (the VSGnome) of Trypanosoma brucei Lister 427. Mol Biochem Parasitol 2014; 195(1): 59-73.
[http://dx.doi.org/10.1016/j.molbiopara.2014.06.004] [PMID: 24992042]
[49]
Marcello L, Barry JD. Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure. Genome Res 2007; 17(9): 1344-52.
[http://dx.doi.org/10.1101/gr.6421207] [PMID: 17652423]
[50]
Hertz-Fowler C, Figueiredo LM, Quail MA, et al. Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS One 2008; 3(10), e3527.
[http://dx.doi.org/10.1371/journal.pone.0003527] [PMID: 18953401]
[51]
Hall JPJ, Wang H, Barry JD. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation. PLoS Pathog 2013; 9(7), e1003502.
[http://dx.doi.org/10.1371/journal.ppat.1003502] [PMID: 23853603]
[52]
Mugnier MR, Cross GAM, Papavasiliou FN. The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science 2015; 347(6229): 1470-3.
[http://dx.doi.org/10.1126/science.aaa4502] [PMID: 25814582]
[53]
Capewell P, Cooper A, Clucas C, Weir W, Macleod A. A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome. Parasitology 2015; 142(S1)(Suppl. 1): S108-19.
[http://dx.doi.org/10.1017/S0031182014000602] [PMID: 25656360]
[54]
Vanhollebeke B, De Muylder G, Nielsen MJ, et al. A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans. Science 2008; 320(5876): 677-81.
[http://dx.doi.org/10.1126/science.1156296] [PMID: 18451305]
[55]
Vanhollebeke B, Pays E. The trypanolytic factor of human serum: many ways to enter the parasite, a single way to kill. Mol Microbiol 2010; 76(4): 806-14.
[http://dx.doi.org/10.1111/j.1365-2958.2010.07156.x] [PMID: 20398209]
[56]
Bullard W, Kieft R, Capewell P, Veitch NJ, Macleod A, Hajduk SL. Haptoglobin-hemoglobin receptor independent killing of African trypanosomes by human serum and trypanosome lytic factors. Virulence 2012; 3(1): 72-6.
[http://dx.doi.org/10.4161/viru.3.1.18295] [PMID: 22286709]
[57]
Drain J, Bishop JR, Hajduk SL. Haptoglobin-related protein mediates trypanosome lytic factor binding to trypanosomes. J Biol Chem 2001; 276(32): 30254-60.
[http://dx.doi.org/10.1074/jbc.M010198200] [PMID: 11352898]
[58]
Green HP, Del Pilar Molina Portela M, St Jean EN, Lugli EB, Raper J. Evidence for a Trypanosoma brucei lipoprotein scavenger receptor. J Biol Chem 2003; 278(1): 422-7.
[http://dx.doi.org/10.1074/jbc.M207215200] [PMID: 12401813]
[59]
Pays E, Vanhollebeke B, Vanhamme L, Paturiaux-Hanocq F, Nolan DP, Pérez-Morga D. The trypanolytic factor of human serum. Nat Rev Microbiol 2006; 4(6): 477-86.
[http://dx.doi.org/10.1038/nrmicro1428] [PMID: 16710327]
[60]
Vanhamme L, Paturiaux-Hanocq F, Poelvoorde P, et al. Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature 2003; 422(6927): 83-7.
[http://dx.doi.org/10.1038/nature01461] [PMID: 12621437]
[61]
Vanhollebeke B, Pays E. The function of apolipoproteins L. Cell Mol Life Sci 2006; 63(17): 1937-44.
[http://dx.doi.org/10.1007/s00018-006-6091-x] [PMID: 16847577]
[62]
Vanwalleghem G, Fontaine F, Lecordier L, et al. Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1. Nat Commun 2015; 6(1): 8078.
[http://dx.doi.org/10.1038/ncomms9078] [PMID: 26307671]
[63]
Rifkin MR. Trypanosoma brucei: biochemical and morphological studies of cytotoxicity caused by normal human serum. Exp Parasitol 1984; 58(1): 81-93.
[http://dx.doi.org/10.1016/0014-4894(84)90023-7] [PMID: 6745390]
[64]
De Greef C, Hamers R. The serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein. Mol Biochem Parasitol 1994; 68(2): 277-84.
[http://dx.doi.org/10.1016/0166-6851(94)90172-4] [PMID: 7739673]
[65]
Xong HV, Vanhamme L, Chamekh M, et al. A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 1998; 95(6): 839-46.
[http://dx.doi.org/10.1016/S0092-8674(00)81706-7] [PMID: 9865701]
[66]
Zoll S, Lane-Serff H, Mehmood S, et al. The structure of serum resistance-associated protein and its implications for human African trypanosomiasis. Nat Microbiol 2018; 3(3): 295-301.
[http://dx.doi.org/10.1038/s41564-017-0085-3] [PMID: 29358741]
[67]
Bart J-M, Cordon-Obras C, Vidal I, et al. Localization of serum resistance-associated protein in Trypanosoma brucei rhodesiense and transgenic Trypanosoma brucei brucei. Cell Microbiol 2015; 17(10): 1523-35.
[http://dx.doi.org/10.1111/cmi.12454] [PMID: 25924022]
[68]
Oli MW, Cotlin LF, Shiflett AM, Hajduk SL. Serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in Trypanosoma brucei. Eukaryot Cell 2006; 5(1): 132-9.
[http://dx.doi.org/10.1128/EC.5.1.132-139.2006] [PMID: 16400175]
[69]
Stephens NA, Hajduk SL. Endosomal localization of the serum resistance-associated protein in African trypanosomes confers human infectivity. Eukaryot Cell 2011; 10(8): 1023-33.
[http://dx.doi.org/10.1128/EC.05112-11] [PMID: 21705681]
[70]
Thomson R, Finkelstein A. Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: relevance to trypanosome lysis. Proc Natl Acad Sci USA 2015; 112(9): 2894-9.
[http://dx.doi.org/10.1073/pnas.1421953112] [PMID: 25730870]
[71]
Wang J, Böhme U, Cross GAM. Structural features affecting variant surface glycoprotein expression in Trypanosoma brucei. Mol Biochem Parasitol 2003; 128(2): 135-45.
[http://dx.doi.org/10.1016/S0166-6851(03)00055-0] [PMID: 12742580]
[72]
DeJesus E, Kieft R, Albright B, Stephens NA, Hajduk SL. A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin-hemoglobin receptor abolishes TLF-1 binding. PLoS Pathog 2013; 9(4), e1003317.
[http://dx.doi.org/10.1371/journal.ppat.1003317] [PMID: 23637606]
[73]
Higgins MK, Tkachenko O, Brown A, Reed J, Raper J, Carrington M. Structure of the trypanosome haptoglobin-hemoglobin receptor and implications for nutrient uptake and innate immunity. Proc Natl Acad Sci USA 2013; 110(5): 1905-10.
[http://dx.doi.org/10.1073/pnas.1214943110] [PMID: 23319650]
[74]
Felu C, Pasture J, Pays E, Pérez-Morga D. Diagnostic potential of a conserved genomic rearrangement in the Trypanosoma brucei gambiense-specific TGSGP locus. Am J Trop Med Hyg 2007; 76(5): 922-9.
[http://dx.doi.org/10.4269/ajtmh.2007.76.922] [PMID: 17488917]
[75]
Gibson W, Nemetschke L, Ndung’u J. Conserved sequence of the TgsGP gene in Group 1 Trypanosoma brucei gambiense. Infect Genet Evol 2010; 10(4): 453-8.
[http://dx.doi.org/10.1016/j.meegid.2010.03.005] [PMID: 20302972]
[76]
Berberof M, Pérez-Morga D, Pays E. A receptor-like flagellar pocket glycoprotein specific to Trypanosoma brucei gambiense. Mol Biochem Parasitol 2001; 113(1): 127-38.
[http://dx.doi.org/10.1016/S0166-6851(01)00208-0] [PMID: 11254961]
[77]
Capewell P, Clucas C, DeJesus E, et al. The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. PLoS Pathog 2013; 9(10), e1003686.
[http://dx.doi.org/10.1371/journal.ppat.1003686] [PMID: 24098129]
[78]
Uzureau P, Uzureau S, Lecordier L, et al. Mechanism of Trypanosoma brucei gambiense resistance to human serum. Nature 2013; 501(7467): 430-4.
[http://dx.doi.org/10.1038/nature12516] [PMID: 23965626]
[79]
Fenn K, Matthews KR. The cell biology of Trypanosoma brucei differentiation. Curr Opin Microbiol 2007; 10(6): 539-46.
[http://dx.doi.org/10.1016/j.mib.2007.09.014] [PMID: 17997129]
[80]
Robertson M. Notes on the life-history of Trypanosoma gambiense, with a brief reference to the cycles of Trypanosoma nanum and Trypanosoma pecorum in Glossina palpalis . Philosophical Transactions of the Royal Society of London Series B, Containing Papers of a Biological Character 1913; 203(294-302): 161-84..
[81]
Turner CMR, Barry JD, Vickerman K. Loss of variable antigen during transformation of Trypanosoma brucei rhodesiense from bloodstream to procyclic forms in the tsetse fly. Parasitol Res 1988; 74(6): 507-11.
[http://dx.doi.org/10.1007/BF00531626] [PMID: 3194363]
[82]
Czichos J, Nonnengaesser C, Overath P. Trypanosoma brucei: cis-aconitate and temperature reduction as triggers of synchronous transformation of bloodstream to procyclic trypomastigotes in vitro. Exp Parasitol 1986; 62(2): 283-91.
[http://dx.doi.org/10.1016/0014-4894(86)90033-0] [PMID: 3743718]
[83]
Hunt M, Brun R, Köhler P. Studies on compounds promoting the in vitro transformation of Trypanosoma brucei from bloodstream to procyclic forms. Parasitol Res 1994; 80(7): 600-6.
[http://dx.doi.org/10.1007/BF00933009] [PMID: 7855126]
[84]
Imbuga MO, Osir EO, Labongo VL, Darji N, Otieno LH. Studies on tsetse midgut factors that induce differentiation of blood-stream Trypanosoma brucei brucei in vitro. Parasitol Res 1992; 78(1): 10-5.
[http://dx.doi.org/10.1007/BF00936174] [PMID: 1584740]
[85]
Sbicego S, Vassella E, Kurath U, Blum B, Roditi I. The use of transgenic Trypanosoma brucei to identify compounds inducing the differentiation of bloodstream forms to procyclic forms. Mol Biochem Parasitol 1999; 104(2): 311-22.
[http://dx.doi.org/10.1016/S0166-6851(99)00157-7] [PMID: 10593184]
[86]
Lehane MJ, Allingham PG, Weglicki P. Composition of the peritrophic matrix of the tsetse fly, Glossina morsitans morsitans. Cell Tissue Res 1996; 283(3): 375-84.
[http://dx.doi.org/10.1007/s004410050548] [PMID: 8593667]
[87]
Ellis DS, Evans DA. Passage of Trypanosoma brucei rhodesiense through the peritrophic membrane of Glossina morsitans morsitans. Nature 1977; 267(5614): 834-5.
[http://dx.doi.org/10.1038/267834a0] [PMID: 895841]
[88]
Berriman M, Ghedin E, Hertz-Fowler C, et al. The genome of the African trypanosome Trypanosoma brucei. Science 2005; 309(5733): 416-22.
[http://dx.doi.org/10.1126/science.1112642] [PMID: 16020726]
[89]
Freeman JC. The penetration of the peritrophic membrane of the tsetse flies by trypanosomes. Acta Trop 1973; 30(4): 347-55.
[PMID: 4149681]
[90]
Freeman JC. The presence of trypanosomes in the ecto-peritrophic space of tsetse flies, half an hour after ingestion of the infective blood meal. Trans R Soc Trop Med Hyg 1970; 64(1): 187-8.
[http://dx.doi.org/10.1016/0035-9203(70)90246-4] [PMID: 5442066]
[91]
Rose C, Casas-Sánchez A, Dyer NA, Solórzano C, Beckett AJ, Middlehurst B, et al. Trypanosoma brucei colonizes the tsetse gut via an immature peritrophic matrix in the proventriculus . Nat Microbiol 2020.http://www.nature.com/articles/s41564-020-0707-z. http://www.nature.com/articles/s41564-020-0707-z
[http://dx.doi.org/10.1038/s41564-020-0707-z]
[92]
Shaw S, DeMarco SF, Rehmann R, et al. Flagellar cAMP signaling controls trypanosome progression through host tissues. Nat Commun 2019; 10(1): 803.
[http://dx.doi.org/10.1038/s41467-019-08696-y] [PMID: 30778051]
[93]
Sharma R, Peacock L, Gluenz E, Gull K, Gibson W, Carrington M. Asymmetric cell division as a route to reduction in cell length and change in cell morphology in trypanosomes. Protist 2008; 159(1): 137-51.
[http://dx.doi.org/10.1016/j.protis.2007.07.004] [PMID: 17931969]
[94]
Van Den Abbeele J, Claes Y, van Bockstaele D, Le Ray D, Coosemans M. Trypanosoma brucei spp. development in the tsetse fly: characterization of the post-mesocyclic stages in the foregut and proboscis. Parasitology 1999; 118(Pt 5): 469-78.
[http://dx.doi.org/10.1017/S0031182099004217] [PMID: 10363280]
[95]
Lewis EA, Langridge WP. Developmental forms of Trypanosoma brucei in the saliva of Glossina pallidipes and Glossina austeni. Ann Trop Med Parasitol 1947; 41(1): 6-13.
[http://dx.doi.org/10.1080/00034983.1947.11685305] [PMID: 20249284]
[96]
Tetley L, Turner CM, Barry JD, Crowe JS, Vickerman K. Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy. J Cell Sci 1987; 87(Pt 2): 363-72.
[PMID: 3654788]
[97]
Tetley L, Vickerman K. Differentiation in Trypanosoma brucei: host-parasite cell junctions and their persistence during acquisition of the variable antigen coat. J Cell Sci 1985; 74(1): 1-19.
[PMID: 4030903]
[98]
Peacock L, Bailey M, Gibson W. Dynamics of gamete production and mating in the parasitic protist Trypanosoma brucei. Parasit Vectors 2016; 9(1): 404.
[http://dx.doi.org/10.1186/s13071-016-1689-9] [PMID: 27439767]
[99]
Rotureau B, Subota I, Buisson J, Bastin P. A new asymmetric division contributes to the continuous production of infective trypanosomes in the tsetse fly. Development 2012; 139(10): 1842-50.
[http://dx.doi.org/10.1242/dev.072611] [PMID: 22491946]
[100]
Sharma R, Gluenz E, Peacock L, Gibson W, Gull K, Carrington M. The heart of darkness: growth and form of Trypanosoma brucei in the tsetse fly. Trends Parasitol 2009; 25(11): 517-24.
[http://dx.doi.org/10.1016/j.pt.2009.08.001] [PMID: 19747880]
[101]
Aksoy S, Weiss BL, Attardo GM. Trypanosome transmission dynamics in tsetse. Curr Opin Insect Sci 2014; 3: 43-9.
[http://dx.doi.org/10.1016/j.cois.2014.07.003] [PMID: 25580379]
[102]
Bruce D, Hamerton AE, Bateman HR, Mackie FP. The development of trypanosoma gambiense in glossina palpalis. Proc R Soc Lond, B 1909; 81(550): 405-14.
[http://dx.doi.org/10.1098/rspb.1909.0041]
[103]
Bruce D. The Croonian Lectures ON TRYPANOSOMES CAUSING DISEASE IN MAN AND DOMESTIC ANIMALS IN CENTRAL AFRICA: Delivered before the Royal College of Physicians of London. BMJ 1915; 2(2846): 91-7.
[http://dx.doi.org/10.1136/bmj.2.2846.91] [PMID: 20767731]
[104]
Desquesnes M, Dia ML. Mechanical transmission of Trypanosoma congolense in cattle by the African tabanid Atylotus agrestis. Exp Parasitol 2003; 105(3-4): 226-31.
[http://dx.doi.org/10.1016/j.exppara.2003.12.014] [PMID: 14990316]
[105]
Mihok S, Maramba O, Munyoki E, Kagoiya J. Mechanical transmission of Trypanosoma spp. by African Stomoxyinae (Diptera: Muscidae). Trop Med Parasitol 1995; 46(2): 103-5.
[PMID: 8525279]
[106]
Roberts LW, Wellde BT, Reardon MJ, Onyango FK. Mechanical transmission of Trypanosoma brucei rhodesiense by Glossina morsitans morsitans (Diptera:Glossinidae). Ann Trop Med Parasitol 1989; 83(Suppl. 1): 127-31.
[http://dx.doi.org/10.1080/00034983.1989.11812417] [PMID: 2619386]
[107]
Robertson M. Notes on the life-history of Trypanosoma gambiense, etc. Proc R Soc Lond, B 1912; 86(584): 66-71.
[http://dx.doi.org/10.1098/rspb.1912.0093]
[108]
Gibson W, Peacock L, Ferris V, Williams K, Bailey M. The use of yellow fluorescent hybrids to indicate mating in Trypanosoma brucei. Parasit Vectors 2008; 1(1): 4.
[http://dx.doi.org/10.1186/1756-3305-1-4] [PMID: 18298832]
[109]
Gibson W, Bailey M. Genetic exchange in Trypanosoma brucei: evidence for meiosis from analysis of a cross between drug-resistant transformants. Mol Biochem Parasitol 1994; 64(2): 241-52.
[http://dx.doi.org/10.1016/0166-6851(94)00017-4] [PMID: 7935602]
[110]
Gibson WC. Analysis of a genetic cross between Trypanosoma brucei rhodesiense and T. b. brucei. Parasitology 1989; 99(Pt 3): 391-402.
[http://dx.doi.org/10.1017/S0031182000059114] [PMID: 2575239]
[111]
Jenni L, Marti S, Schweizer J, et al. Hybrid formation between African trypanosomes during cyclical transmission. Nature 1986; 322(6075): 173-5.
[http://dx.doi.org/10.1038/322173a0] [PMID: 3724860]
[112]
MacLeod A, Tweedie A, McLellan S, et al. Allelic segregation and independent assortment in T. brucei crosses: proof that the genetic system is Mendelian and involves meiosis. Mol Biochem Parasitol 2005; 143(1): 12-9.
[http://dx.doi.org/10.1016/j.molbiopara.2005.04.009] [PMID: 15941603]
[113]
Sternberg J, Turner CMR, Wells JM, Ranford-Cartwright LC, Le Page RWF, Tait A. Gene exchange in African trypanosomes: frequency and allelic segregation. Mol Biochem Parasitol 1989; 34(3): 269-79.
[http://dx.doi.org/10.1016/0166-6851(89)90056-X] [PMID: 2567494]
[114]
Turner CMR, Sternberg J, Buchanan N, Smith E, Hide G, Tait A. Evidence that the mechanism of gene exchange in Trypanosoma brucei involves meiosis and syngamy. Parasitology 1990; 101(Pt 3): 377-86.
[http://dx.doi.org/10.1017/S0031182000060571] [PMID: 1982633]
[115]
Peacock L, Ferris V, Sharma R, et al. Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly. Proc Natl Acad Sci USA 2011; 108(9): 3671-6.
[http://dx.doi.org/10.1073/pnas.1019423108] [PMID: 21321215]
[116]
Peacock L, Bailey M, Carrington M, Gibson W. Meiosis and haploid gametes in the pathogen Trypanosoma brucei. Curr Biol 2014; 24(2): 181-6.
[http://dx.doi.org/10.1016/j.cub.2013.11.044] [PMID: 24388851]
[117]
Imhof S, Fragoso C, Hemphill A, et al. Flagellar membrane fusion and protein exchange in trypanosomes; a new form of cell-cell communication? F1000 Res 2016; 5: 682.
[http://dx.doi.org/10.12688/f1000research.8249.1] [PMID: 27239276]
[118]
Gibson W, Crow M, Kearns J. Kinetoplast DNA minicircles are inherited from both parents in genetic crosses of Trypanosoma brucei. Parasitol Res 1997; 83(5): 483-8.
[http://dx.doi.org/10.1007/s004360050284] [PMID: 9197397]
[119]
Gibson W, Garside L. Kinetoplast DNA minicircles are inherited from both parents in genetic hybrids of Trypanosoma brucei. Mol Biochem Parasitol 1990; 42(1): 45-53.
[http://dx.doi.org/10.1016/0166-6851(90)90111-X] [PMID: 2233899]
[120]
Turner CMR, Hide G, Buchanan N, Tait A. Trypanosoma brucei: inheritance of kinetoplast DNA maxicircles in a genetic cross and their segregation during vegetative growth. Exp Parasitol 1995; 80(2): 234-41.
[http://dx.doi.org/10.1006/expr.1995.1029] [PMID: 7895834]
[121]
Gibson W. Liaisons dangereuses: sexual recombination among pathogenic trypanosomes. Res Microbiol 2015; 166(6): 459-66.
[http://dx.doi.org/10.1016/j.resmic.2015.05.005] [PMID: 26027775]
[122]
Tait A, Turner CMR, Le Page RWF, Wells JM. Genetic evidence that metacyclic forms of Trypanosoma brucei are diploid. Mol Biochem Parasitol 1989; 37(2): 247-55.
[http://dx.doi.org/10.1016/0166-6851(89)90156-4] [PMID: 2575222]
[123]
Peacock L, Ferris V, Bailey M, Gibson W. Mating compatibility in the parasitic protist Trypanosoma brucei. Parasit Vectors 2014; 7(1): 78.
[http://dx.doi.org/10.1186/1756-3305-7-78] [PMID: 24559099]
[124]
Koffi M, De Meeûs T, Bucheton B, et al. Population genetics of Trypanosoma brucei gambiense, the agent of sleeping sickness in Western Africa. Proc Natl Acad Sci USA 2009; 106(1): 209-14.
[http://dx.doi.org/10.1073/pnas.0811080106] [PMID: 19106297]
[125]
Morrison LJ, Tait A, McCormack G, et al. Trypanosoma brucei gambiense Type 1 populations from human patients are clonal and display geographical genetic differentiation. Infect Genet Evol 2008; 8(6): 847-54.
[http://dx.doi.org/10.1016/j.meegid.2008.08.005] [PMID: 18790085]
[126]
Dean S, Sunter JD, Wheeler RJ. TrypTag.org: A Trypanosome Genome-wide Protein Localisation Resource. Trends Parasitol 2017; 33(2): 80-2.
[http://dx.doi.org/10.1016/j.pt.2016.10.009] [PMID: 27863903]
[127]
Sherwin T, Gull K. The cell division cycle of Trypanosoma brucei brucei: timing of event markers and cytoskeletal modulations. Philos Trans R Soc Lond B Biol Sci 1989; 323(1218): 573-88.
[http://dx.doi.org/10.1098/rstb.1989.0037] [PMID: 2568647]
[128]
Robinson DR, Sherwin T, Ploubidou A, Byard EH, Gull K. Microtubule polarity and dynamics in the control of organelle positioning, segregation, and cytokinesis in the trypanosome cell cycle. J Cell Biol 1995; 128(6): 1163-72.
[http://dx.doi.org/10.1083/jcb.128.6.1163] [PMID: 7896879]
[129]
Sherwin T, Gull K. Visualization of detyrosination along single microtubules reveals novel mechanisms of assembly during cytoskeletal duplication in trypanosomes. Cell 1989; 57(2): 211-21.
[http://dx.doi.org/10.1016/0092-8674(89)90959-8] [PMID: 2649249]
[130]
Wheeler RJ, Scheumann N, Wickstead B, Gull K, Vaughan S. Cytokinesis in Trypanosoma brucei differs between bloodstream and tsetse trypomastigote forms: implications for microtubule-based morphogenesis and mutant analysis. Mol Microbiol 2013; 90(6): 1339-55.
[http://dx.doi.org/10.1111/mmi.12436] [PMID: 24164479]
[131]
Sun SY, Kaelber JT, Chen M, et al. Flagellum couples cell shape to motility in Trypanosoma brucei. Proc Natl Acad Sci USA 2018; 115(26): E5916-25.
[http://dx.doi.org/10.1073/pnas.1722618115] [PMID: 29891682]
[132]
Hertz-Fowler C, Ersfeld K, Gull K. CAP5.5, a life-cycle-regulated, cytoskeleton-associated protein is a member of a novel family of calpain-related proteins in Trypanosoma brucei. Mol Biochem Parasitol 2001; 116(1): 25-34.
[http://dx.doi.org/10.1016/S0166-6851(01)00296-1] [PMID: 11463463]
[133]
May SF, Peacock L, Almeida Costa CI, et al. The Trypanosoma brucei AIR9-like protein is cytoskeleton-associated and is required for nucleus positioning and accurate cleavage furrow placement. Mol Microbiol 2012; 84(1): 77-92.
[http://dx.doi.org/10.1111/j.1365-2958.2012.08008.x] [PMID: 22329999]
[134]
Portman N, Gull K. Identification of paralogous life-cycle stage specific cytoskeletal proteins in the parasite Trypanosoma brucei. PLoS One 2014; 9(9), e106777.
[http://dx.doi.org/10.1371/journal.pone.0106777] [PMID: 25180513]
[135]
Vedrenne C, Giroud C, Robinson DR, et al. Two Related Subpellicular Cytoskeleton-associated Proteins in Trypanosoma brucei Stabilize Microtubules. 2002.
[136]
Dong X, Lim TK, Lin Q, He CY. Basal Body Protein TbSAF1 Is Required for Microtubule Quartet Anchorage to the Basal Bodies in Trypanosoma brucei. MBio 2020; 11(3)https://mbio.asm.org/content/11/3/e00668-20
[137]
Lacomble S, Vaughan S, Gadelha C, et al. Three-dimensional cellular architecture of the flagellar pocket and associated cytoskeleton in trypanosomes revealed by electron microscope tomography. J Cell Sci 2009; 122(Pt 8): 1081-90.
[http://dx.doi.org/10.1242/jcs.045740] [PMID: 19299460]
[138]
Lacomble S, Vaughan S, Deghelt M, Moreira-Leite FF, Gull K. A Trypanosoma brucei protein required for maintenance of the flagellum attachment zone and flagellar pocket ER domains. Protist 2012; 163(4): 602-15.
[http://dx.doi.org/10.1016/j.protis.2011.10.010] [PMID: 22186015]
[139]
Gheiratmand L, Brasseur A, Zhou Q, He CY. Biochemical characterization of the bi-lobe reveals a continuous structural network linking the bi-lobe to other single-copied organelles in Trypanosoma brucei. J Biol Chem 2013; 288(5): 3489-99.
[http://dx.doi.org/10.1074/jbc.M112.417428] [PMID: 23235159]
[140]
Langousis G, Hill KL. Motility and more: the flagellum of Trypanosoma brucei. Nat Rev Microbiol 2014; 12(7): 505-18.
[http://dx.doi.org/10.1038/nrmicro3274] [PMID: 24931043]
[141]
Alsford S, Turner DJ, Obado SO, et al. High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome. Genome Res 2011; 21(6): 915-24.
[http://dx.doi.org/10.1101/gr.115089.110] [PMID: 21363968]
[142]
Branche C, Kohl L, Toutirais G, Buisson J, Cosson J, Bastin P. Conserved and specific functions of axoneme components in trypanosome motility. J Cell Sci 2006; 119(Pt 16): 3443-55.
[http://dx.doi.org/10.1242/jcs.03078] [PMID: 16882690]
[143]
Broadhead R, Dawe HR, Farr H, et al. Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 2006; 440(7081): 224-7.
[http://dx.doi.org/10.1038/nature04541] [PMID: 16525475]
[144]
Ralston KS, Hill KL. Trypanin, a component of the flagellar Dynein regulatory complex, is essential in bloodstream form African trypanosomes. PLoS Pathog 2006; 2(9), e101.
[http://dx.doi.org/10.1371/journal.ppat.0020101] [PMID: 17009870]
[145]
Rotureau B, Ooi C-P, Huet D, Perrot S, Bastin P. Forward motility is essential for trypanosome infection in the tsetse fly. Cell Microbiol 2014; 16(3): 425-33.
[http://dx.doi.org/10.1111/cmi.12230] [PMID: 24134537]
[146]
Shimogawa MM, Ray SS, Kisalu N, et al. Parasite motility is critical for virulence of African trypanosomes. Sci Rep 2018; 8(1): 9122.
[http://dx.doi.org/10.1038/s41598-018-27228-0] [PMID: 29904094]
[147]
Bertiaux E, Morga B, Blisnick T, Rotureau B, Bastin P. A Grow-and-Lock Model for the Control of Flagellum Length in Trypanosomes. Curr Biol 2018; 28(23): 3802-3814.e3.
[http://dx.doi.org/10.1016/j.cub.2018.10.031] [PMID: 30449671]
[148]
Atkins M, Týč J, Shafiq S, et al. CEP164C regulates flagellum length in stable flagella. J Cell Biol 2021; 220(1), e2020011160.
[149]
Vaughan S, Gull K. Basal body structure and cell cycle-dependent biogenesis in Trypanosoma brucei. Cilia 2016; 5(1): 5.
[http://dx.doi.org/10.1186/s13630-016-0023-7] [PMID: 26862392]
[150]
Atkins M, Týč J, Shafiq S, et al. A key regulatory protein for flagellum length control in stable flagella. bioRxiv 2019 In press
[151]
Harmer J, Towers K, Addison M, Vaughan S, Ginger ML, McKean PG. A centriolar FGR1 oncogene partner-like protein required for paraflagellar rod assembly, but not axoneme assembly in African trypanosomes. Open Biol 2018; 8(7), 170218.
[http://dx.doi.org/10.1098/rsob.170218] [PMID: 30045883]
[152]
Dute R, Kung C. Ultrastructure of the proximal region of somatic cilia in Paramecium tetraurelia. J Cell Biol 1978; 78(2): 451-64.
[http://dx.doi.org/10.1083/jcb.78.2.451] [PMID: 690175]
[153]
Ounjai P, Kim KD, Liu H, et al. Architectural insights into a ciliary partition. Curr Biol 2013; 23(4): 339-44.
[http://dx.doi.org/10.1016/j.cub.2013.01.029] [PMID: 23375896]
[154]
Dean S, Moreira-Leite F, Gull K. Basalin is an evolutionarily unconstrained protein revealed via a conserved role in flagellum basal plate function. eLife 2019; 8, e42282.
[http://dx.doi.org/10.7554/eLife.42282] [PMID: 30810527]
[155]
Dean S, Moreira-Leite F, Varga V, Gull K. Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes. Proc Natl Acad Sci USA 2016; 113(35): E5135-43.
[http://dx.doi.org/10.1073/pnas.1604258113] [PMID: 27519801]
[156]
Reiter JF, Blacque OE, Leroux MR. The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization. EMBO Rep 2012; 13(7): 608-18.
[http://dx.doi.org/10.1038/embor.2012.73] [PMID: 22653444]
[157]
Trépout S, Tassin A-M, Marco S, Bastin P. STEM tomography analysis of the trypanosome transition zone. J Struct Biol 2018; 202(1): 51-60.
[http://dx.doi.org/10.1016/j.jsb.2017.12.005] [PMID: 29248600]
[158]
Vickerman K. The mode of attachment of Trypanosoma vivax in the proboscis of the tsetse fly Glossina fuscipes: an ultrastructural study of the epimastigote stage of the trypanosome. J Protozool 1973; 20(3): 394-404.
[http://dx.doi.org/10.1111/j.1550-7408.1973.tb00909.x] [PMID: 4731343]
[159]
Vickerman K, Tetley L. Flagellar Surfaces of Parasitic Protozoa and Their Role in Attachment. Ciliary and Flagellar Membranes 1990; pp. 267-304.
[http://dx.doi.org/10.1007/978-1-4613-0515-6_11]
[160]
Gadelha C, Rothery S, Morphew M, McIntosh JR, Severs NJ, Gull K. Membrane domains and flagellar pocket boundaries are influenced by the cytoskeleton in African trypanosomes. Proc Natl Acad Sci USA 2009; 106(41): 17425-30.
[http://dx.doi.org/10.1073/pnas.0909289106] [PMID: 19805090]
[161]
Höög JL, Lacomble S, O’Toole ET, Hoenger A, McIntosh JR, Gull K. Modes of flagellar assembly in Chlamydomonas reinhardtii and Trypanosoma brucei.Schekman R, editor eLife. 2014; 3: p. e01479..
[162]
Summers KE, Gibbons IR. Adenosine triphosphate-induced sliding of tubules in trypsin-treated flagella of sea-urchin sperm. Proc Natl Acad Sci USA 1971; 68(12): 3092-6.
[http://dx.doi.org/10.1073/pnas.68.12.3092] [PMID: 5289252]
[163]
Smith EF, Yang P. The radial spokes and central apparatus: mechano-chemical transducers that regulate flagellar motility. Cell Motil Cytoskeleton 2004; 57(1): 8-17.
[http://dx.doi.org/10.1002/cm.10155] [PMID: 14648553]
[164]
Höög JL, Bouchet-Marquis C, McIntosh JR, Hoenger A, Gull K. Cryo-electron tomography and 3-D analysis of the intact flagellum in Trypanosoma brucei. J Struct Biol 2012; 178(2): 189-98.
[http://dx.doi.org/10.1016/j.jsb.2012.01.009] [PMID: 22285651]
[165]
Koyfman AY, Schmid MF, Gheiratmand L, et al. Structure of Trypanosoma brucei flagellum accounts for its bihelical motion. Proc Natl Acad Sci USA 2011; 108(27): 11105-8.
[http://dx.doi.org/10.1073/pnas.1103634108] [PMID: 21690369]
[166]
Portman N, Gull K. The paraflagellar rod of kinetoplastid parasites: from structure to components and function. Int J Parasitol 2010; 40(2): 135-48.
[http://dx.doi.org/10.1016/j.ijpara.2009.10.005] [PMID: 19879876]
[167]
Deflorin J, Rudolf M, Seebeck T. The major components of the paraflagellar rod of Trypanosoma brucei are two similar, but distinct proteins which are encoded by two different gene loci. J Biol Chem 1994; 269(46): 28745-51.
[PMID: 7961827]
[168]
Schlaeppi K, Deflorin J, Seebeck T. The major component of the paraflagellar rod of Trypanosoma brucei is a helical protein that is encoded by two identical, tandemly linked genes. J Cell Biol 1989; 109(4 Pt 1): 1695-709.
[http://dx.doi.org/10.1083/jcb.109.4.1695] [PMID: 2793936]
[169]
Portman N, Lacomble S, Thomas B, McKean PG, Gull K. Combining RNA interference mutants and comparative proteomics to identify protein components and dependences in a eukaryotic flagellum. J Biol Chem 2009; 284(9): 5610-9.
[http://dx.doi.org/10.1074/jbc.M808859200] [PMID: 19074134]
[170]
Oberholzer M, Marti G, Baresic M, Kunz S, Hemphill A, Seebeck T. The Trypanosoma brucei cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence. FASEB J 2007; 21(3): 720-31.
[http://dx.doi.org/10.1096/fj.06-6818com] [PMID: 17167070]
[171]
Pullen TJ, Ginger ML, Gaskell SJ, Gull K. Protein targeting of an unusual, evolutionarily conserved adenylate kinase to a eukaryotic flagellum. Mol Biol Cell 2004; 15(7): 3257-65.
[http://dx.doi.org/10.1091/mbc.e04-03-0217] [PMID: 15146060]
[172]
Ridgley E, Webster P, Patton C, Ruben L. Calmodulin-binding properties of the paraflagellar rod complex from Trypanosoma brucei. Mol Biochem Parasitol 2000; 109(2): 195-201.
[http://dx.doi.org/10.1016/S0166-6851(00)00246-2] [PMID: 10960180]
[173]
Bastin P, MacRae TH, Francis SB, Matthews KR, Gull K. Flagellar morphogenesis: protein targeting and assembly in the paraflagellar rod of trypanosomes. Mol Cell Biol 1999; 19(12): 8191-200.
[http://dx.doi.org/10.1128/MCB.19.12.8191] [PMID: 10567544]
[174]
Alves AA, Gabriel HB, Bezerra MJR, de Souza W, Vaughan S, Cunha-e-Silva NL, et al. Control of assembly of extra-axonemal structures: the paraflagellar rod of trypanosomes. J Cell Sci 2020; 133(10)https://jcs.biologists.org/content/133/10/jcs242271
[175]
Bastin P, Pullen TJ, Sherwin T, Gull K. Protein transport and flagellum assembly dynamics revealed by analysis of the paralysed trypanosome mutant snl-1. J Cell Sci 1999; 112(Pt 21): 3769-77.
[PMID: 10523512]
[176]
Bastin P, Sherwin T, Gull K. Paraflagellar rod is vital for trypanosome motility. Nature 1998; 391(6667): 548-8.
[http://dx.doi.org/10.1038/35300] [PMID: 9468133]
[177]
Hughes LC, Ralston KS, Hill KL, Zhou ZH. Three-dimensional structure of the Trypanosome flagellum suggests that the paraflagellar rod functions as a biomechanical spring. PLoS One 2012; 7(1), e25700.
[http://dx.doi.org/10.1371/journal.pone.0025700] [PMID: 22235240]
[178]
Sunter JD, Gull K. The Flagellum Attachment Zone: ‘The Cellular Ruler’ of Trypanosome Morphology. Trends Parasitol 2016; 32(4): 309-24.
[http://dx.doi.org/10.1016/j.pt.2015.12.010] [PMID: 26776656]
[179]
Hayes P, Varga V, Olego-Fernandez S, Sunter J, Ginger ML, Gull K. Modulation of a cytoskeletal calpain-like protein induces major transitions in trypanosome morphology. J Cell Biol 2014; 206(3): 377-84.
[http://dx.doi.org/10.1083/jcb.201312067] [PMID: 25092656]
[180]
Sun SY, Wang C, Yuan YA, He CY. An intracellular membrane junction consisting of flagellum adhesion glycoproteins links flagellum biogenesis to cell morphogenesis in Trypanosoma brucei. J Cell Sci 2013; 126(Pt 2): 520-31.
[http://dx.doi.org/10.1242/jcs.113621] [PMID: 23178943]
[181]
Sunter JD, Benz C, Andre J, et al. Modulation of flagellum attachment zone protein FLAM3 and regulation of the cell shape in Trypanosoma brucei life cycle transitions. J Cell Sci 2015; 128(16): 3117-30.
[http://dx.doi.org/10.1242/jcs.171645] [PMID: 26148511]
[182]
Sunter JD, Varga V, Dean S, Gull K. A dynamic coordination of flagellum and cytoplasmic cytoskeleton assembly specifies cell morphogenesis in trypanosomes. J Cell Sci 2015; 128(8): 1580-94.
[http://dx.doi.org/10.1242/jcs.166447] [PMID: 25736289]
[183]
LaCount DJ, Barrett B, Donelson JE. Trypanosoma brucei FLA1 is required for flagellum attachment and cytokinesis. J Biol Chem 2002; 277(20): 17580-8.
[http://dx.doi.org/10.1074/jbc.M200873200] [PMID: 11877446]
[184]
Nozaki T, Haynes PA, Cross GAM. Characterization of the Trypanosoma brucei homologue of a Trypanosoma cruzi flagellum-adhesion glycoprotein. Mol Biochem Parasitol 1996; 82(2): 245-55.
[http://dx.doi.org/10.1016/0166-6851(96)02741-7] [PMID: 8946390]
[185]
Vaughan S, Kohl L, Ngai I, Wheeler RJ, Gull K. A repetitive protein essential for the flagellum attachment zone filament structure and function in Trypanosoma brucei. Protist 2008; 159(1): 127-36.
[http://dx.doi.org/10.1016/j.protis.2007.08.005] [PMID: 17945531]
[186]
Allen CL, Goulding D, Field MC. Clathrin-mediated endocytosis is essential in Trypanosoma brucei. EMBO J 2003; 22(19): 4991-5002.
[http://dx.doi.org/10.1093/emboj/cdg481] [PMID: 14517238]
[187]
Borst P, Fairlamb AH. Surface receptors and transporters of Trypanosoma brucei. Annu Rev Microbiol 1998; 52(1): 745-78.
[http://dx.doi.org/10.1146/annurev.micro.52.1.745] [PMID: 9891812]
[188]
Hung C-H, Qiao X, Lee P-T, Lee MG-S. Clathrin-dependent targeting of receptors to the flagellar pocket of procyclic-form Trypanosoma brucei. Eukaryot Cell 2004; 3(4): 1004-14.
[http://dx.doi.org/10.1128/EC.3.4.1004-1014.2004] [PMID: 15302833]
[189]
Henley GL, Lee CM, Takeuchi A. Electron microscopy observations on Trypanosoma brucei: freeze-cleaving and thin-sectioning study of the apical part of the flagellar pocket. Z Parasitenkd 1978; 55(3): 181-7.
[http://dx.doi.org/10.1007/BF00390368] [PMID: 695819]
[190]
Bonhivers M, Nowacki S, Landrein N, Robinson DR. Biogenesis of the trypanosome endo-exocytotic organelle is cytoskeleton mediated. PLoS Biol 2008; 6(5), e105.
[http://dx.doi.org/10.1371/journal.pbio.0060105] [PMID: 18462016]
[191]
Florimond C, Sahin A, Vidilaseris K, et al. BILBO1 is a scaffold protein of the flagellar pocket collar in the pathogen Trypanosoma brucei. PLoS Pathog 2015; 11(3), e1004654.
[http://dx.doi.org/10.1371/journal.ppat.1004654] [PMID: 25822645]
[192]
Vidilaseris K, Lesigang J, Morriswood B, Dong G. Assembly mechanism of Trypanosoma brucei BILBO1 at the flagellar pocket collar. Commun Integr Biol 2015; 8(1), e992739.
[http://dx.doi.org/10.4161/19420889.2014.992739] [PMID: 26844754]
[193]
Albisetti A, Florimond C, Landrein N, et al. Interaction between the flagellar pocket collar and the hook complex via a novel microtubule-binding protein in Trypanosoma brucei. PLoS Pathog 2017; 13(11), e1006710.
[http://dx.doi.org/10.1371/journal.ppat.1006710] [PMID: 29091964]
[194]
Morriswood B. Form, Fabric, and Function of a Flagellum-Associated Cytoskeletal Structure. Cells 2015; 4(4): 726-47.
[http://dx.doi.org/10.3390/cells4040726] [PMID: 26540076]
[195]
Morriswood B, Havlicek K, Demmel L, et al. Novel bilobe components in Trypanosoma brucei identified using proximity-dependent biotinylation. Eukaryot Cell 2013; 12(2): 356-67.
[http://dx.doi.org/10.1128/EC.00326-12] [PMID: 23264645]
[196]
Morriswood B, Schmidt K. A MORN Repeat Protein Facilitates Protein Entry into the Flagellar Pocket of Trypanosoma brucei. Eukaryot Cell 2015; 14(11): 1081-93.
[http://dx.doi.org/10.1128/EC.00094-15] [PMID: 26318396]
[197]
Jakob M, Hoffmann A, Amodeo S, Peitsch C, Zuber B, Ochsenreiter T. Mitochondrial growth during the cell cycle of Trypanosoma brucei bloodstream forms. Sci Rep 2016; 6(1): 36565.
[http://dx.doi.org/10.1038/srep36565] [PMID: 27874016]
[198]
Flynn IW, Bowman IBR. The metabolism of carbohydrate by pleomorphic African trypanosomes. Comp Biochem Physiol B 1973; 45(1): 25-42.
[http://dx.doi.org/10.1016/0305-0491(73)90281-2] [PMID: 4719992]
[199]
Jensen RE, Englund PT. Network news: the replication of kinetoplast DNA. Annu Rev Microbiol 2012; 66: 473-91.
[http://dx.doi.org/10.1146/annurev-micro-092611-150057] [PMID: 22994497]
[200]
Lukes J, Guilbride DL, Votýpka J, Zíková A, Benne R, Englund PT. Kinetoplast DNA network: evolution of an improbable structure. Eukaryot Cell 2002; 1(4): 495-502.
[http://dx.doi.org/10.1128/EC.1.4.495-502.2002] [PMID: 12455998]
[201]
Benne R, Van den Burg J, Brakenhoff JPJ, Sloof P, Van Boom JH, Tromp MC. Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 1986; 46(6): 819-26.
[http://dx.doi.org/10.1016/0092-8674(86)90063-2] [PMID: 3019552]
[202]
Shapiro TA, Englund PT. The structure and replication of kinetoplast DNA. Annu Rev Microbiol 1995; 49(1): 117-43.
[http://dx.doi.org/10.1146/annurev.mi.49.100195.001001] [PMID: 8561456]
[203]
Aphasizheva I, Alfonzo J, Carnes J, et al. Lexis and Grammar of Mitochondrial RNA Processing in Trypanosomes. Trends Parasitol 2020; 36(4): 337-55.
[http://dx.doi.org/10.1016/j.pt.2020.01.006] [PMID: 32191849]
[204]
Hajduk S, Ochsenreiter T. RNA editing in kinetoplastids. RNA Biol 2010; 7(2): 229-36.
[http://dx.doi.org/10.4161/rna.7.2.11393] [PMID: 20220308]
[205]
Abu-Elneel K, Robinson DR, Drew ME, Englund PT, Shlomai J. Intramitochondrial localization of universal minicircle sequence-binding protein, a trypanosomatid protein that binds kinetoplast minicircle replication origins. J Cell Biol 2001; 153(4): 725-34.
[http://dx.doi.org/10.1083/jcb.153.4.725] [PMID: 11352934]
[206]
Drew ME, Englund PT. Intramitochondrial location and dynamics of Crithidia fasciculata kinetoplast minicircle replication intermediates. J Cell Biol 2001; 153(4): 735-44.
[http://dx.doi.org/10.1083/jcb.153.4.735] [PMID: 11352935]
[207]
Ogbadoyi EO, Robinson DR, Gull K. A high-order trans-membrane structural linkage is responsible for mitochondrial genome positioning and segregation by flagellar basal bodies in trypanosomes. Mol Biol Cell 2003; 14(5): 1769-79.
[http://dx.doi.org/10.1091/mbc.e02-08-0525] [PMID: 12802053]
[208]
Robinson DR, Gull K. Basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle. Nature 1991; 352(6337): 731-3.
[http://dx.doi.org/10.1038/352731a0] [PMID: 1876188]
[209]
Gluenz E, Shaw MK, Gull K. Structural asymmetry and discrete nucleic acid subdomains in the Trypanosoma brucei kinetoplast. Mol Microbiol 2007; 64(6): 1529-39.
[http://dx.doi.org/10.1111/j.1365-2958.2007.05749.x] [PMID: 17511811]
[210]
Schneider A, Ochsenreiter T. Failure is not an option - mitochondrial genome segregation in trypanosomes. J Cell Sci 2018; 131(18)https://jcs.biologists.org/content/131/18/jcs221820
[211]
Amodeo S, Kalichava A, Fradera-Sola A, Bertiaux-Lequoy E, Guichard P, Butter F, et al. Characterization of the Novel Mitochondrial Genome Segregation Factor TAP110 in Trypanosoma brucei. bioRxiv 2020.
[212]
Trikin R, Doiron N, Hoffmann A, et al. TAC102 Is a Novel Component of the Mitochondrial Genome Segregation Machinery in Trypanosomes. PLoS Pathog 2016; 12(5), e1005586.
[http://dx.doi.org/10.1371/journal.ppat.1005586] [PMID: 27168148]
[213]
Hoffmann A, Käser S, Jakob M, et al. Molecular model of the mitochondrial genome segregation machinery in Trypanosoma brucei. Proc Natl Acad Sci USA 2018; 115(8): E1809-18.
[http://dx.doi.org/10.1073/pnas.1716582115] [PMID: 29434039]
[214]
Schnarwiler F, Niemann M, Doiron N, et al. Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance. Proc Natl Acad Sci USA 2014; 111(21): 7624-9.
[http://dx.doi.org/10.1073/pnas.1404854111] [PMID: 24821793]
[215]
Gualdrón-López M, Brennand A, Hannaert V, et al. When, how and why glycolysis became compartmentalised in the Kinetoplastea. A new look at an ancient organelle. Int J Parasitol 2012; 42(1): 1-20.
[http://dx.doi.org/10.1016/j.ijpara.2011.10.007] [PMID: 22142562]
[216]
Opperdoes FR, Borst P. Localization of nine glycolytic enzymes in a microbody-like organelle in Trypanosoma brucei: the glycosome. FEBS Lett 1977; 80(2): 360-4.
[http://dx.doi.org/10.1016/0014-5793(77)80476-6] [PMID: 142663]
[217]
Misset O, Bos OJ, Opperdoes FR. Glycolytic enzymes of Trypanosoma brucei. Simultaneous purification, intraglycosomal concentrations and physical properties. Eur J Biochem 1986; 157(2): 441-53.
[http://dx.doi.org/10.1111/j.1432-1033.1986.tb09687.x] [PMID: 2940090]
[218]
Hughes L, Borrett S, Towers K, Starborg T, Vaughan S. Patterns of organelle ontogeny through a cell cycle revealed by whole-cell reconstructions using 3D electron microscopy. J Cell Sci 2017; 130(3): 637-47.
[http://dx.doi.org/10.1242/jcs.198887] [PMID: 28049718]
[219]
Tetley L, Vickerman K. The glycosomes of trypanosomes: number and distribution as revealed by electron spectroscopic imaging and 3-D reconstruction. J Microsc 1991; 162(Pt 1): 83-90.
[http://dx.doi.org/10.1111/j.1365-2818.1991.tb03118.x] [PMID: 1870115]
[220]
Hart DT, Misset O, Edwards SW, Opperdoes FR. A comparison of the glycosomes (microbodies) isolated from Trypanosoma brucei bloodstream form and cultured procyclic trypomastigotes. Mol Biochem Parasitol 1984; 12(1): 25-35.
[http://dx.doi.org/10.1016/0166-6851(84)90041-0] [PMID: 6749187]
[221]
Bakker BM, Mensonides FIC, Teusink B, van Hoek P, Michels PAM, Westerhoff HV. Compartmentation protects trypanosomes from the dangerous design of glycolysis. Proc Natl Acad Sci USA 2000; 97(5): 2087-92.
[http://dx.doi.org/10.1073/pnas.030539197] [PMID: 10681445]
[222]
Bakker BM, Michels PAM, Opperdoes FR, Westerhoff HV. Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes. J Biol Chem 1997; 272(6): 3207-15.
[http://dx.doi.org/10.1074/jbc.272.6.3207] [PMID: 9013556]
[223]
Bakker BM, Westerhoff HV, Michels PAM. Regulation and control of compartmentalized glycolysis in bloodstream form Trypanosoma brucei. J Bioenerg Biomembr 1995; 27(5): 513-25.
[http://dx.doi.org/10.1007/BF02110191] [PMID: 8718456]
[224]
Szöör B, Haanstra JR, Gualdrón-López M, Michels PA. Evolution, dynamics and specialized functions of glycosomes in metabolism and development of trypanosomatids. Curr Opin Microbiol 2014; 22: 79-87.
[http://dx.doi.org/10.1016/j.mib.2014.09.006] [PMID: 25460800]
[225]
Allmann S, Bringaud F. Glycosomes: A comprehensive view of their metabolic roles in T. brucei. Int J Biochem Cell Biol 2017; 85: 85-90.
[http://dx.doi.org/10.1016/j.biocel.2017.01.015] [PMID: 28179189]
[226]
Szöőr B, Simon DV, Rojas F, et al. Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation. mBio 2019; 10(4)https://mbio.asm.org/content/10/4/e00875-19
[227]
Nosengo N. Can you teach old drugs new tricks? Nature 2016; 534(7607): 314-6.
[http://dx.doi.org/10.1038/534314a] [PMID: 27306171]
[228]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[229]
DNDi. Target Product Profile - Sleeping Sickness. 2009. Available at:. https://www.dndi.org/diseases-projects/hat/hat-target-product-profile/
[230]
Altamura F, Rajesh R, Catta-Preta CMC, Moretti NS, Cestari I. The current drug discovery landscape for trypanosomiasis and leishmaniasis: Challenges and strategies to identify drug targets.Drug Development Research. https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.21664
[231]
Deeks ED. Fexinidazole: First Global Approval. Drugs 2019; 79(2): 215-20.
[http://dx.doi.org/10.1007/s40265-019-1051-6] [PMID: 30635838]
[232]
Fairlamb AH. Fexinidazole for the treatment of human African trypanosomiasis. Drugs Today (Barc) 2019; 55(11): 705-12.
[http://dx.doi.org/10.1358/dot.2019.55.11.3068795] [PMID: 31840685]
[233]
Gilbert IH. Target-based drug discovery for human African trypanosomiasis: selection of molecular target and chemical matter. Parasitology 2014; 141(1): 28-36.
[http://dx.doi.org/10.1017/S0031182013001017] [PMID: 23931634]
[234]
Alsford S, Eckert S, Baker N, et al. High-throughput decoding of antitrypanosomal drug efficacy and resistance. Nature 2012; 482(7384): 232-6.
[http://dx.doi.org/10.1038/nature10771] [PMID: 22278056]
[235]
Baker N, Alsford S, Horn D. Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6. Mol Biochem Parasitol 2011; 176(1): 55-7.
[http://dx.doi.org/10.1016/j.molbiopara.2010.11.010] [PMID: 21093499]
[236]
Begolo D, Erben E, Clayton C. Drug target identification using a trypanosome overexpression library. Antimicrob Agents Chemother 2014; 58(10): 6260-4.
[http://dx.doi.org/10.1128/AAC.03338-14] [PMID: 25049244]
[237]
Siegel TN, Gunasekera K, Cross GAM, Ochsenreiter T. Gene expression in Trypanosoma brucei: lessons from high-throughput RNA sequencing. Trends Parasitol 2011; 27(10): 434-41.
[http://dx.doi.org/10.1016/j.pt.2011.05.006] [PMID: 21737348]
[238]
Diaz R, Luengo-Arratta SA, Seixas JD, et al. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign. PLoS Negl Trop Dis 2014; 8(10), e3253.
[http://dx.doi.org/10.1371/journal.pntd.0003253] [PMID: 25340575]
[239]
Peña I, Pilar Manzano M, Cantizani J, et al. New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource. Sci Rep 2015; 5: 8771.
[http://dx.doi.org/10.1038/srep08771] [PMID: 25740547]
[240]
Woodland A, Thompson S, Cleghorn LAT, et al. Discovery of Inhibitors of Trypanosoma brucei by Phenotypic Screening of a Focused Protein Kinase Library. ChemMedChem 2015; 10(11): 1809-20.
[http://dx.doi.org/10.1002/cmdc.201500300] [PMID: 26381210]
[241]
Rotureau B, Morales MA, Bastin P, Späth GF. The flagellum-mitogen-activated protein kinase connection in Trypanosomatids: a key sensory role in parasite signalling and development? Cell Microbiol 2009; 11(5): 710-8.
[http://dx.doi.org/10.1111/j.1462-5822.2009.01295.x] [PMID: 19207727]
[242]
Stortz JA, Serafim TD, Alsford S, et al. Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei. PLoS Pathog 2017; 13(7), e1006477.
[http://dx.doi.org/10.1371/journal.ppat.1006477] [PMID: 28742144]
[243]
Parsons M, Worthey EA, Ward PN, Mottram JC. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi. BMC Genomics 2005; 6: 127.
[http://dx.doi.org/10.1186/1471-2164-6-127] [PMID: 16164760]
[244]
Nett IRE, Martin DMA, Miranda-Saavedra D, et al. The phosphoproteome of bloodstream form Trypanosoma brucei, causative agent of African sleeping sickness. Mol Cell Proteomics 2009; 8(7): 1527-38.
[http://dx.doi.org/10.1074/mcp.M800556-MCP200] [PMID: 19346560]
[245]
Urbaniak MD, Martin DMA, Ferguson MAJ. Global quantitative SILAC phosphoproteomics reveals differential phosphorylation is widespread between the procyclic and bloodstream form lifecycle stages of Trypanosoma brucei. J Proteome Res 2013; 12(5): 2233-44.
[http://dx.doi.org/10.1021/pr400086y] [PMID: 23485197]
[246]
Jones NG, Thomas EB, Brown E, Dickens NJ, Hammarton TC, Mottram JC. Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen. PLoS Pathog 2014; 10(1), e1003886.
[http://dx.doi.org/10.1371/journal.ppat.1003886] [PMID: 24453978]
[247]
Mackey ZB, Koupparis K, Nishino M, McKerrow JH. High-throughput analysis of an RNAi library identifies novel kinase targets in Trypanosoma brucei. Chem Biol Drug Des 2011; 78(3): 454-63.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01156.x] [PMID: 21668652]
[248]
Urbaniak MD, Mathieson T, Bantscheff M, et al. Chemical proteomic analysis reveals the drugability of the kinome of Trypanosoma brucei. ACS Chem Biol 2012; 7(11): 1858-65.
[http://dx.doi.org/10.1021/cb300326z] [PMID: 22908928]
[249]
Fernandez-Cortes F, Serafim TD, Wilkes JM, et al. RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse. Sci Rep 2017; 7(1): 6156.
[http://dx.doi.org/10.1038/s41598-017-06501-8] [PMID: 28733613]
[250]
Saldivia M, Rao SPS, Fang E, et al. Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors. Nat Microbiol 2020; 5(10): 1207-16.
[251]
Emmer BT, Souther C, Toriello KM, Olson CL, Epting CL, Engman DM. Identification of a palmitoyl acyltransferase required for protein sorting to the flagellar membrane. J Cell Sci 2009; 122(Pt 6): 867-74.
[http://dx.doi.org/10.1242/jcs.041764] [PMID: 19240115]
[252]
Godsel LM, Engman DM. Flagellar protein localization mediated by a calcium-myristoyl/palmitoyl switch mechanism. EMBO J 1999; 18(8): 2057-65.
[http://dx.doi.org/10.1093/emboj/18.8.2057] [PMID: 10205160]
[253]
Brown RWB, Sharma AI, Engman DM. Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence. Crit Rev Biochem Mol Biol 2017; 52(2): 145-62.
[http://dx.doi.org/10.1080/10409238.2017.1287161] [PMID: 28228066]
[254]
Emmer BT, Nakayasu ES, Souther C, et al. Global analysis of protein palmitoylation in African trypanosomes. Eukaryot Cell 2011; 10(3): 455-63.
[http://dx.doi.org/10.1128/EC.00248-10] [PMID: 21193548]
[255]
Colasante C, Ellis M, Ruppert T, Voncken F. Comparative proteomics of glycosomes from bloodstream form and procyclic culture form Trypanosoma brucei brucei. Proteomics 2006; 6(11): 3275-93.
[http://dx.doi.org/10.1002/pmic.200500668] [PMID: 16622829]
[256]
Güther MLS, Urbaniak MD, Tavendale A, Prescott A, Ferguson MAJ. High-confidence glycosome proteome for procyclic form Trypanosoma brucei by epitope-tag organelle enrichment and SILAC proteomics. J Proteome Res 2014; 13(6): 2796-806.
[http://dx.doi.org/10.1021/pr401209w] [PMID: 24792668]
[257]
Vertommen D, Van Roy J, Szikora J-P, Rider MH, Michels PAM, Opperdoes FR. Differential expression of glycosomal and mitochondrial proteins in the two major life-cycle stages of Trypanosoma brucei. Mol Biochem Parasitol 2008; 158(2): 189-201.
[http://dx.doi.org/10.1016/j.molbiopara.2007.12.008] [PMID: 18242729]
[258]
Brimacombe KR, Walsh MJ, Liu L, et al. Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase. ACS Med Chem Lett 2013; 5(1): 12-7.
[http://dx.doi.org/10.1021/ml400259d] [PMID: 24900769]
[259]
Flaherty DP, Harris MT, Schroeder CE, et al. Optimization and Evaluation of Antiparasitic Benzamidobenzoic Acids as Inhibitors of Kinetoplastid Hexokinase 1. ChemMedChem 2017; 12(23): 1994-2005.
[http://dx.doi.org/10.1002/cmdc.201700592] [PMID: 29105342]
[260]
Eisenthal R, Cornish-Bowden A. Prospects for antiparasitic drugs. The case of Trypanosoma brucei, the causative agent of African sleeping sickness. J Biol Chem 1998; 273(10): 5500-5.
[http://dx.doi.org/10.1074/jbc.273.10.5500] [PMID: 9488673]
[261]
Field MC, Horn D, Fairlamb AH, et al. Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nat Rev Microbiol 2017; 15(4): 217-31.
[http://dx.doi.org/10.1038/nrmicro.2016.193] [PMID: 28239154]
[262]
Dawidowski M, Emmanouilidis L, Kalel VC, et al. Inhibitors of PEX14 disrupt protein import into glycosomes and kill Trypanosoma parasites. Science 2017; 355(6332): 1416-20.
[http://dx.doi.org/10.1126/science.aal1807] [PMID: 28360328]
[263]
Kalel VC, Mäser P, Sattler M, Erdmann R, Popowicz GM. Come, sweet death: targeting glycosomal protein import for antitrypanosomal drug development. Curr Opin Microbiol 2018; 46: 116-22.
[http://dx.doi.org/10.1016/j.mib.2018.11.003] [PMID: 30481613]
[264]
Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 1996; 65: 801-47.
[http://dx.doi.org/10.1146/annurev.bi.65.070196.004101] [PMID: 8811196]
[265]
Steverding D. The proteasome as a potential target for chemotherapy of African trypanosomiasis. Drug Dev Res 2007; 68(5): 205-12.
[http://dx.doi.org/10.1002/ddr.20188]
[266]
Li Z, Zou C-B, Yao Y, et al. An easily dissociated 26 S proteasome catalyzes an essential ubiquitin-mediated protein degradation pathway in Trypanosoma brucei. J Biol Chem 2002; 277(18): 15486-98.
[http://dx.doi.org/10.1074/jbc.M109029200] [PMID: 11854272]
[267]
Glenn RJ, Pemberton AJ, Royle HJ, et al. Trypanocidal effect of α′,β′-epoxyketones indicates that trypanosomes are particularly sensitive to inhibitors of proteasome trypsin-like activity. Int J Antimicrob Agents 2004; 24(3): 286-9.
[http://dx.doi.org/10.1016/j.ijantimicag.2004.02.023] [PMID: 15325434]
[268]
Khare S, Nagle AS, Biggart A, et al. Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature 2016; 537(7619): 229-33.
[http://dx.doi.org/10.1038/nature19339] [PMID: 27501246]
[269]
Mutomba MC, To WY, Hyun WC, Wang CC. Inhibition of proteasome activity blocks cell cycle progression at specific phase boundaries in African trypanosomes. Mol Biochem Parasitol 1997; 90(2): 491-504.
[http://dx.doi.org/10.1016/S0166-6851(97)00197-7] [PMID: 9476796]
[270]
Nkemngu NJ, Rosenkranz V, Wink M, Steverding D, Steverding D. Antitrypanosomal activities of proteasome inhibitors. Antimicrob Agents Chemother 2002; 46(6): 2038-40.
[http://dx.doi.org/10.1128/AAC.46.6.2038-2040.2002] [PMID: 12019136]
[271]
Steverding D, Wang X. Trypanocidal activity of the proteasome inhibitor and anti-cancer drug bortezomib. Parasit Vectors 2009; 2(1): 29.
[http://dx.doi.org/10.1186/1756-3305-2-29] [PMID: 19583840]
[272]
Vaughan S, Gull K. The trypanosome flagellum. J Cell Sci 2003; 116(Pt 5): 757-9.
[http://dx.doi.org/10.1242/jcs.00287] [PMID: 12571273]
[273]
Oberholzer M, Langousis G, Nguyen HT, et al. Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei. Molecular & Cellular Proteomics 2011; 10(10)https://www.mcponline.org/content/10/10/M111.010538
[274]
Huang G, Ulrich PN, Storey M, et al. Proteomic analysis of the acidocalcisome, an organelle conserved from bacteria to human cells. PLoS Pathog 2014; 10(12), e1004555.
[http://dx.doi.org/10.1371/journal.ppat.1004555] [PMID: 25503798]
[275]
Crozier TWM, Tinti M, Wheeler RJ, Ly T, Ferguson MAJ, Lamond AI. Proteomic Analysis of the Cell Cycle of Procylic Form Trypanosoma brucei. Mol Cell Proteomics 2018; 17(6): 1184-95.
[http://dx.doi.org/10.1074/mcp.RA118.000650] [PMID: 29555687]
[276]
Gunasekera K, Wüthrich D, Braga-Lagache S, Heller M, Ochsenreiter T. Proteome remodelling during development from blood to insect-form Trypanosoma brucei quantified by SILAC and mass spectrometry. BMC Genomics 2012; 13: 556.
[http://dx.doi.org/10.1186/1471-2164-13-556] [PMID: 23067041]
[277]
Butter F, Bucerius F, Michel M, Cicova Z, Mann M, Janzen CJ. Comparative proteomics of two life cycle stages of stable isotope-labeled Trypanosoma brucei reveals novel components of the parasite’s host adaptation machinery. Mol Cell Proteomics 2013; 12(1): 172-9.
[http://dx.doi.org/10.1074/mcp.M112.019224] [PMID: 23090971]
[278]
Varga V, Moreira-Leite F, Portman N, Gull K. Protein diversity in discrete structures at the distal tip of the trypanosome flagellum. Proc Natl Acad Sci USA 2017; 114(32): E6546-55.
[http://dx.doi.org/10.1073/pnas.1703553114] [PMID: 28724725]
[279]
Hart SR, Lau KW, Hao Z, et al. Analysis of the trypanosome flagellar proteome using a combined electron transfer/collisionally activated dissociation strategy. J Am Soc Mass Spectrom 2009; 20(2): 167-75.
[http://dx.doi.org/10.1016/j.jasms.2008.08.014] [PMID: 18930411]
[280]
Price HP, Hodgkinson MR, Curwen RS, et al. The orthologue of Sjögren’s syndrome nuclear autoantigen 1 (SSNA1) in Trypanosoma brucei is an immunogenic self-assembling molecule. PLoS One 2012; 7(2), e31842.
[http://dx.doi.org/10.1371/journal.pone.0031842] [PMID: 22363749]
[281]
Subota I, Julkowska D, Vincensini L, et al. Proteomic analysis of intact flagella of procyclic Trypanosoma brucei cells identifies novel flagellar proteins with unique sub-localization and dynamics. Mol Cell Proteomics 2014; 13(7): 1769-86.
[http://dx.doi.org/10.1074/mcp.M113.033357] [PMID: 24741115]
[282]
Niemann M, Wiese S, Mani J, et al. Mitochondrial outer membrane proteome of Trypanosoma brucei reveals novel factors required to maintain mitochondrial morphology. Mol Cell Proteomics 2013; 12(2): 515-28.
[http://dx.doi.org/10.1074/mcp.M112.023093] [PMID: 23221899]
[283]
Fisk JC, Li J, Wang H, Aletta JM, Qu J, Read LK. Proteomic analysis reveals diverse classes of arginine methylproteins in mitochondria of trypanosomes. Mol Cell Proteomics 2013; 12(2): 302-11.
[http://dx.doi.org/10.1074/mcp.M112.022533] [PMID: 23152538]
[284]
Panigrahi AK, Ogata Y, Zíková A, et al. A comprehensive analysis of Trypanosoma brucei mitochondrial proteome. Proteomics 2009; 9(2): 434-50.
[http://dx.doi.org/10.1002/pmic.200800477] [PMID: 19105172]
[285]
Goos C, Dejung M, Janzen CJ, Butter F, Kramer S. The nuclear proteome of Trypanosoma brucei. PLoS One 2017; 12(7), e0181884.
[http://dx.doi.org/10.1371/journal.pone.0181884] [PMID: 28727848]
[286]
Dejung M, Subota I, Bucerius F, et al. Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei. PLoS Pathog 2016; 12(2), e1005439.
[http://dx.doi.org/10.1371/journal.ppat.1005439] [PMID: 26910529]
[287]
Shimogawa MM, Saada EA, Vashisht AA, Barshop WD, Wohlschlegel JA, Hill KL. Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei. Mol Cell Proteomics 2015; 14(7): 1977-88.
[http://dx.doi.org/10.1074/mcp.M114.045146] [PMID: 25963835]
[288]
Gadelha C, Zhang W, Chamberlain JW, Chait BT, Wickstead B, Field MC. Architecture of a Host-Parasite Interface: Complex Targeting Mechanisms Revealed Through Proteomics. Mol Cell Proteomics 2015; 14(7): 1911-26.
[http://dx.doi.org/10.1074/mcp.M114.047647] [PMID: 25931509]
[289]
Colasante C, Voncken F, Manful T, et al. Proteins and lipids of glycosomal membranes from Leishmania tarentolae and Trypanosoma brucei. F1000 Res 2013; 2: 27.
[http://dx.doi.org/10.12688/f1000research.2-27.v1] [PMID: 24358884]
[290]
Vaughan S, Shaw M, Gull K. A post-assembly structural modification to the lumen of flagellar microtubule doublets. Curr Biol 2006; 16(12): R449-50.
[http://dx.doi.org/10.1016/j.cub.2006.05.041] [PMID: 16781996]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy