25 years of African trypanosome research: From description to molecular dissection and new drug discovery

Molecular and Biochemical Parasitology

Volumn 200, Issue 1-2, 2015, Pages 30-40

  Matthews, Keith R ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Molecular parasitology; Trypanosoma brucei; Trypanosome

Indexed keywords

ANTIGEN; ANTITRYPANOSOMAL AGENT; DNA DIRECTED RNA POLYMERASE; DOUBLE STRANDED RNA; EFLORNITHINE; ETHIDIUM BROMIDE; FEXINIDAZOLE; KINETOPLAST DNA; RNA POLYMERASE II; ANTIPROTOZOAL AGENT;

AFRICAN TRYPANOSOMIASIS; ANTIGENIC VARIATION; CELL DIFFERENTIATION; CELL STRUCTURE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENETIC SELECTION; HUMAN; LIFE CYCLE; MITOCHONDRIAL GENE; MOLECULAR BIOLOGY; MOLECULAR PARASITOLOGY; NONHUMAN; PARASITISM; PARASITOLOGY; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; TRYPANOSOMA; TRYPANOSOMA BRUCEI; TRYPANOSOMIASIS; ANIMAL; DRUG DEVELOPMENT; DRUG EFFECTS; GENETICS; HISTORY; PHYSIOLOGY; TRENDS; TRYPANOSOMA BRUCEI BRUCEI; TRYPANOSOMIASIS, AFRICAN;

TRYPANOSOMA BRUCEI;

ANIMALS; ANTIPROTOZOAL AGENTS; DRUG DISCOVERY; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; TRYPANOSOMA BRUCEI BRUCEI; TRYPANOSOMIASIS, AFRICAN;

EID: 84930818034     PISSN: 01666851     EISSN: 18729428     Source Type: Journal    
DOI: 10.1016/j.molbiopara.2015.01.006     Document Type: Review

References (196)

1. P. Borst, and V. Nussenzweig Molecular parasitology at Woods Hole Cell 71 6 1992 895 899
2. M. Berriman, E. Ghedin, C. Hertz-Fowler, G. Blandin, H. Renauld, and D.C. Bartholomeu The genome of the African trypanosome Trypanosoma brucei Science 309 5733 2005 416 422
3. J.M. Kooter, d.-S.-H.J. van, R. Wagter, C.E. d'Oliveira, d.-H.-F. van, and P.J. Johnson The anatomy and transcription of a telomeric expression site for variant-specific surface antigens in T. Brucei Cell 51 2 1987 261 272
4. D.F. Cully, H.S. Ip, and G.A. Cross Coordinate transcription of variant surface glycoprotein genes and an expression site associated gene family in Trypanosoma brucei Cell 42 1 1985 173 182
5. E. Pays, D. Tebabi, A. Pays, H. Coquelet, P. Revelard, and D. Salmon The genes and transcripts of an antigen gene expression site from T. Brucei Cell 57 5 1989 835 845
6. F.J. van Deursen, S.K. Shahi, C.M. Turner, C. Hartmann, C. Guerra-Giraldez, and K.R. Matthews Characterisation of the growth and differentiation in vivo and in vitro-of bloodstream-form Trypanosoma brucei strain TREU 927 Mol Biochem Parasitol 112 2 2001 163 171
7. M. Becker, N. Aitcheson, E. Byles, B. Wickstead, E. Louis, and G. Rudenko Isolation of the repertoire of VSG expression site containing telomeres of Trypanosoma brucei 427 using transformation-associated recombination in yeast Genome Res 14 11 2004 2319 2329
8. R. Young, J.E. Taylor, A. Kurioka, M. Becker, E.J. Louis, and G. Rudenko Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. B. Brucei and T. equiperdum BMC Genomics 9 2008 385
9. D. Freymann, J. Down, M. Carrington, I. Roditi, M. Turner, and D. Wiley 2.9 A resolution structure of the N-terminal domain of a variant surface glycoprotein from Trypanosoma brucei J Mol Biol 216 1 1990 141 160
10. A. Schwede, N. Jones, M. Engstler, and M. Carrington The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes Mol Biochem Parasitol 175 2 2011 201 204
11. M.A.J. Ferguson, S.W. Homans, R.A. Dwek, and T.W. Rademacher Glycosyl-phosphatidylinositol moiety that anchors Trypanosoma brucei variant surface glycoprotein to the membrane Science 239 4841 1988 753 759
12. W.J. Masterson, J. Raper, T.L. Doering, G.W. Hart, and P.T. Englund Fatty acid remodeling: a novel reaction sequence in the biosynthesis of trypanosome glycosyl phosphatidylinositol membrane anchors Cell 62 1 1990 73 80
13. W.J. Masterson, T.L. Doering, G.W. Hart, and P.T. Englund A novel pathway for glycan assembly: biosynthesis of the glycosyl-phosphatidylinositol anchor of the trypanosome variant surface glycoprotein Cell 56 5 1989 793 800
14. M.A. Ferguson, J.S. Brimacombe, J.R. Brown, A. Crossman, A. Dix, and R.A. Field The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness Biochim Biophys Acta 1455 2-3 1999 327 340
15. T.K. Smith, D.K. Sharma, A. Crossman, J.S. Brimacombe, and M.A. Ferguson Selective inhibitors of the glycosylphosphatidylinositol biosynthetic pathway of Trypanosoma brucei EMBO J 18 21 1999 5922 5930
16. K.L. Martin, and T.K. Smith The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream-form Trypanosoma brucei is dependent on the de novo synthesis of inositol Mol Microbiol 61 1 2006 89 105
17. M. Engstler, L. Thilo, F. Weise, C.G. Grunfelder, H. Schwarz, and M. Boshart Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein in Trypanosoma brucei J Cell Sci 117 Pt 7 2004 1105 1115
18. M. Engstler, P. Pfohl, S. Herminghaus, M. Boshart, G. Wiegerttjes, and N. Heddergott Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes Cell 131 2007 505 515
19. J. Zomerdijk, M. Ouellette, A. Ten Asbroek, R. Kieft, A.M.M. Bommer, and C.E. Clayton The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei EMBO J 9 9 1990 2791 2801
20. P.J. Johnson, J.M. Kooter, and P. Borst Inactivation of transcription by UV irradiation of T. Brucei provides evidence for a multicistronic transcription unit including a VSG gene Cell 51 2 1987 273 281
21. R. Evers, A. Hammer, J. Kock, W. Jess, P. Borst, and S. Memet Trypanosoma brucei contains two RNA polymerase II largest subunit genes with an altered C-terminal domain Cell 56 4 1989 585 597
22. J.M. Kooter, and P. Borst Alpha-amanitin-insensitive transcription of variant surface glycoprotein genes provides further evidence for discontinuous transcription in trypanosomes Nucleic Acids Res 12 24 1984 9457 9472
23. G. Rudenko, D. Bishop, K. Gottesdiener, and d.-P.-L.H. Van Alpha-amanitin resistant transcription of protein coding genes in insect and bloodstream form Trypanosoma brucei EMBO J 8 13 1989 4259 4263
24. J. Zomerdijk, R. Kieft, P.G. Shiels, and P. Borst Alpha-amanitin-resistant transcription units in trypanosomes: a comparison of promoter sequences for a VSG gene expression site and for the ribosomal RNA genes Nucleic Acids Res 19 19 1991 5153 5158
25. A. Gunzl, T. Bruderer, G. Laufer, B. Schimanski, L.C. Tu, and H.M. Chung RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei Eukaryot Cell 2 3 2003 542 551
26. T.N. Nguyen, B. Schimanski, A. Zahn, B. Klumpp, and A. Gunzl Purification of an eight subunit RNA polymerase I complex in Trypanosoma brucei Mol Biochem Parasitol 149 1 2006 27 37
27. P. Borst, W. Bitter, P.A. Blundell, I. Chaves, M. Cross, and H. Gerrits Control of VSG gene expression sites in Trypanosoma brucei Mol Biochem Parasitol 91 1 1998 67 76
28. E. Pays Expression of variant-specific antigen genes in African trypanosomes Biol Cell 64 2 1988 121 130
29. L.H. Van der Ploeg, D. Valerio, T. De Lange, A. Bernards, P. Borst, and F.G. Grosveld An analysis of cosmid clones of nuclear DNA from Trypanosoma brucei shows that the genes for variant surface glycoproteins are clustered in the genome Nucleic Acids Res 10 19 1982 5905 5923
30. J.D. Barry, L. Marcello, L.J. Morrison, A.F. Read, K. Lythgoe, and N. Jones What the genome sequence is revealing about trypanosome antigenic variation Biochem Soc Trans 33 Pt 5 2005 986 989
31. L. Marcello, and J.D. Barry 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 17 9 2007 1344 1352
32. J.E. Taylor, and G. Rudenko Switching trypanosome coats: what's in the wardrobe? Trends Genet 22 11 2006 614 620
33. M. Navarro, and K. Gull A polI transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei Nature 414 6865 2001 759 763
34. X. Yang, L.M. Figueiredo, A. Espinal, E. Okubo, and B. Li RAP1 is essential for silencing telomeric variant surface glycoprotein genes in Trypanosoma brucei Cell 137 1 2009 99 109
35. M.L. Povelones, E. Gluenz, M. Dembek, K. Gull, and G. Rudenko Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei PLoS Pathog 8 11 2012 e1003010
36. K. Hughes, M. Wand, L. Foulston, R. Young, K. Harley, and S. Terry A novel ISWI is involved in VSG expression site downregulation in African trypanosomes EMBO J 26 9 2007 2400 2410
37. Q.P. Wang, T. Kawahara, and D. Horn Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes Mol Microbiol 77 5 2010 1237 1245
38. D. Landeira, and M. Navarro Nuclear repositioning of the VSG promoter during developmental silencing in Trypanosoma brucei J Cell Biol 176 2 2007 133 139
39. D. Salmon, M. Geuskens, F. Hanocq, Q.-J. Hanocq, D. Nolan, and L. Ruben A novel heterodimeric transferrin receptor encoded by a pair of VSG expression site-associated genes in T. Brucei Cell 78 1 1994 75 86
40. W. Bitter, H. Gerrits, R. Kieft, and P. Borst The role of transferrin-receptor variation in the host range of Trypanosoma brucei Nature 391 6666 1998 499 502
41. D. Steverding The significance of transferrin receptor variation in Trypanosoma brucei Trends Parasitol 19 3 2003 125 127
42. P. Paindavoine, S. Rolin, A.-S. Van, M. Geuskens, J.C. Jauniaux, and C. Dinsart A gene from the variant surface glycoprotein expression site encodes one of several transmembrane adenylate cyclases located on the flagellum of Trypanosoma brucei Mol Cell Biol 12 3 1992 1218 1225
43. D. Salmon, G. Vanwalleghem, Y. Morias, J. Denoeud, C. Krumbholz, and F. Lhomme Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host Science 337 6093 2012 463 466
44. C. Batram, N.G. Jones, C.J. Janzen, S.M. Markert, and M. Engstler Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei Elife 3 2014 e02324
45. M. Hoek, and G.A. Cross Expression-site-associated-gene-8 (ESAG8) is not required for regulation of the VSG expression site in Trypanosoma brucei Mol Biochem Parasitol 117 2 2001 211 215
46. M. Hoek, M. Engstler, and G.A. Cross Expression-site-associated gene 8 (ESAG8) of Trypanosoma brucei is apparently essential and accumulates in the nucleolus J Cell Sci 113 Pt 22 2000 3959 3968
47. G.-C. De, H. Imberechts, G. Matthyssens, M.-N. Van, and R. Hamers A gene expressed only in serum-resistant variants of Trypanosoma brucei rhodesiense Mol Biochem Parasitol 36 2 1989 169 176
48. C. De Greef, and R. Hamers The serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein Mol Biochem Parasitol 68 2 1994 277 284
49. H.V. Xong, L. Vanhamme, M. Chamekh, C.E. Chimfwembe, J. Van Den Abbeele, and A. Pays A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense Cell 95 6 1998 839 846
50. S.C. Welburn, K. Picozzi, E.M. Fevre, P.G. Coleman, M. Odiit, and M. Carrington Identification of human-infective trypanosomes in animal reservoir of sleeping sickness in Uganda by means of serum-resistance-associated (SRA) gene Lancet 358 9298 2001 2017 2019
51. M. Radwanska, M. Chamekh, L. Vanhamme, F. Claes, S. Magez, and E. Magnus The serum resistance-associated gene as a diagnostic tool for the detection of Trypanosoma brucei rhodesiense Am J Trop Med Hyg 67 6 2002 684 690
52. B. Vanhollebeke, G. De Muylder, M.J. Nielsen, A. Pays, P. Tebabi, and M. Dieu A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans Science 320 5876 2008 677 681
53. J. Raper, V. Nussenzweig, and S. Tomlinson The main lytic factor of Trypanosoma brucei brucei in normal human serum is not high density lipoprotein J Exp Med 183 3 1996 1023 1029
54. B. Vanhollebeke, and E. Pays The trypanolytic factor of human serum: many ways to enter the parasite, a single way to kill Mol Microbiol 76 4 2010 806 814
55. L. Vanhamme, F. Paturiaux-Hanocq, P. Poelvoorde, D.P. Nolan, L. Lins, and J. Van Den Abbeele Apolipoprotein L-I is the trypanosome lytic factor of human serum Nature 422 6927 2003 83 87
56. B. Vanhollebeke, M.J. Nielsen, Y. Watanabe, P. Truc, L. Vanhamme, and K. Nakajima Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum Proc Natl Acad Sci U S A 104 10 2007 4118 4123
57. D. Perez-Morga, B. Vanhollebeke, F. Paturiaux-Hanocq, D.P. Nolan, L. Lins, and F. Homble Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes Science 309 5733 2005 469 472
58. M.W. Oli, L.F. Cotlin, A.M. Shiflett, and S.L. Hajduk Serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in Trypanosoma brucei Eukaryot Cell 5 1 2006 132 139
59. P. Capewell, C. Clucas, E. DeJesus, R. Kieft, S. Hajduk, and N. Veitch The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense PLoS Pathog 9 10 2013 e1003686
60. P. Uzureau, S. Uzureau, L. Lecordier, F. Fontaine, P. Tebabi, and F. Homble Mechanism of Trypanosoma brucei gambiense resistance to human serum Nature 501 7467 2013 430 434
61. E. Pays, B. Vanhollebeke, P. Uzureau, L. Lecordier, and D. Perez-Morga The molecular arms race between African trypanosomes and humans Nat Rev Microbiol 12 8 2014 575 584
62. R. Thomson, P. Molina-Portela, H. Mott, M. Carrington, and J. Raper Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes Proc Natl Acad Sci U S A 106 46 2009 19509 19514
63. R. Thomson, G. Genovese, C. Canon, D. Kovacsics, M.K. Higgins, and M. Carrington Evolution of the primate trypanolytic factor APOL1 Proc Natl Acad Sci U S A 111 20 2014 E2130 E2139
64. G. Genovese, D.J. Friedman, M.D. Ross, L. Lecordier, P. Uzureau, and B.I. Freedman Association of trypanolytic ApoL1 variants with kidney disease in African Americans Science 329 5993 2010 841 845
65. T. Sherwin, and K. Gull The cell division cycle of Trypanosoma brucei brucei: timing of event markers and cytoskeletal modulations Philos Trans R Soc Lond B: Biol Sci 323 1218 1989 573 588
66. R. Woodward, and K. Gull Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei J Cell Sci 95 Pt 1 1990 49 57
67. M.L. Ferguson, A.F. Torri, M.-D. Perez, D.C. Ward, and P.T. Englund Kinetoplast DNA replication: mechanistic differences between Trypanosoma brucei and Crithidia fasciculata J Cell Biol 126 3 1994 631 639
68. M. Ferguson, A.F. Torri, D.C. Ward, and P.T. Englund In situ hybridization to the Crithidia fasciculata kinetoplast reveals two antipodal sites involved in kinetoplast DNA replication Cell 70 4 1992 621 629
69. E.O. Ogbadoyi, D.R. Robinson, and K. Gull A high-order trans-membrane structural linkage is responsible for mitochondrial genome positioning and segregation by flagellar basal bodies in trypanosomes Mol Biol Cell 14 5 2003 1769 1779
70. F. Schnarwiler, M. Niemann, N. Doiron, A. Harsman, S. Kaser, and J. Mani Trypanosomal TAC40 constitutes a novel subclass of mitochondrial beta-barrel proteins specialized in mitochondrial genome inheritance Proc Natl Acad Sci U S A 111 21 2014 7624 7629
71. A.M. Clayton, J.L. Guler, M.L. Povelones, E. Gluenz, K. Gull, and T.K. Smith Depletion of mitochondrial acyl carrier protein in bloodstream-form Trypanosoma brucei causes a kinetoplast segregation defect Eukaryot Cell 10 3 2011 286 292
72. Z. Zhao, M.E. Lindsay, A. Roy Chowdhury, D.R. Robinson, and P.T. Englund p166: a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation EMBO J 27 1 2008 143 154
73. T. Ochsenreiter, and S.L. Hajduk Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria generates protein diversity EMBO Rep 7 11 2006 1128 1133
74. S. Dean, M.K. Gould, C.E. Dewar, and A.C. Schnaufer Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes Proc Natl Acad Sci U S A 110 36 2013 14741 14746
75. D.H. Lai, H. Hashimi, Z.R. Lun, F.J. Ayala, and J. Lukes Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. Brucei Proc Natl Acad Sci U S A 105 6 2008 1999 2004
76. L.H.T. van der Ploeg, D.C. Schwartz, C.R. Cantor, and P. Borst Antigenic variation in Trypanosoma brucei analyzed by electrophoretic separation of chromosome-sized DNA molecules Cell 37 1 1984 77 84
77. L.H.T. Van der Ploeg, C.S. Smith, R.I. Polvere, and K.M. Gottesdiener Improved separation of chromosome-sized DNA from Trypanosoma brucei: stock 427-60 Nucleic Acids Res 17 8 1989 3217 3227
78. K. Ersfeld, and K. Gull Partitioning of large and minichromosomes in Trypanosoma brucei Science 276 5312 1997 611 614
79. B. Akiyoshi, and K. Gull Discovery of unconventional kinetochores in kinetoplastids Cell 156 6 2014 1247 1258
80. C. Tiengwe, C.A. Marques, and R. McCulloch Nuclear DNA replication initiation in kinetoplastid parasites: new insights into an ancient process Trends Parasitol 30 1 2014 27 36
81. C. Tiengwe, L. Marcello, H. Farr, N. Dickens, S. Kelly, and M. Swiderski Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei Cell Rep 2 1 2012 185 197
82. B. Morga, and P. Bastin Getting to the heart of intraflagellar transport using Trypanosoma and Chlamydomonas models: the strength is in their differences Cilia 2 1 2013 16
83. S. Vaughan, and K. Gull The trypanosome flagellum J Cell Sci 116 Pt 5 2003 757 759
84. J.L. Hoog, S. Lacomble, E.T. O'Toole, A. Hoenger, J.R. McIntosh, and K. Gull Modes of flagellar assembly in Chlamydomonas reinhardtii and Trypanosoma brucei Elife 3 2014 e01479
85. P. Bastin, T. Sherwin, and K. Gull Paraflagellar rod is vital for trypanosome motility Nature 391 6667 1998 548
86. F.F. Moreira-Leite, T. Sherwin, L. Kohl, and K. Gull A trypanosome structure involved in transmitting cytoplasmic information during cell division Science 294 5542 2001 610 612
87. R.J. Wheeler, N. Scheumann, B. Wickstead, K. Gull, and S. Vaughan Cytokinesis in Trypanosoma brucei differs between bloodstream and tsetse trypomastigote forms: implications for microtubule-based morphogenesis and mutant analysis Mol Microbiol 90 6 2013 1339 1355
88. M. Bonhivers, S. Nowacki, N. Landrein, and D.R. Robinson Biogenesis of the trypanosome endo-exocytotic organelle is cytoskeleton mediated PLoS Biol 6 5 2008 e105
89. L. Hughes, K. Towers, T. Starborg, K. Gull, and S. Vaughan A cell-body groove housing the new flagellum tip suggests an adaptation of cellular morphogenesis for parasitism in the bloodstream form of Trypanosoma brucei J Cell Sci 126 Pt 24 2013 5748 5757
90. C.Y. He, M. Pypaert, and G. Warren Golgi duplication in Trypanosoma brucei requires Centrin2 Science 310 5751 2005 1196 1198
91. C.Y. He, H.H. Ho, J. Malsam, C. Chalouni, C.M. West, and E. Ullu Golgi duplication in Trypanosoma brucei J Cell Biol 165 3 2004 313 321
92. J.S. Silverman, and J.D. Bangs Form and function in the trypanosomal secretory pathway Curr Opin Microbiol 15 4 2012 463 468
93. P.T. Manna, C. Boehm, K.F. Leung, S.K. Natesan, and M.C. Field Life and times: synthesis, trafficking, and evolution of VSG Trends Parasitol 30 5 2014 251 258
94. M. Pusnik, O. Schmidt, A.J. Perry, S. Oeljeklaus, M. Niemann, and B. Warscheid Mitochondrial preprotein translocase of trypanosomatids has a bacterial origin Curr Biol 21 20 2011 1738 1743
95. R. Docampo, D.A. Scott, A.E. Vercesi, and S.N. Moreno Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi Biochem J 310 Pt 3 1995 1005 1012
96. R. Docampo, V. Jimenez, N. Lander, Z.H. Li, and S. Niyogi New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists Int Rev Cell Mol Biol 305 2013 69 113
97. R. Docampo, V. Jimenez, S. King-Keller, Z.H. Li, and S.N. Moreno The role of acidocalcisomes in the stress response of Trypanosoma cruzi Adv Parasitol 75 2011 307 324
98. G. Huang, P.J. Bartlett, A.P. Thomas, S.N. Moreno, and R. Docampo Acidocalcisomes of Trypanosoma brucei have an inositol 1,4,5-trisphosphate receptor that is required for growth and infectivity Proc Natl Acad Sci U S A 110 5 2013 1887 1892
99. K. Ziegelbauer, M. Quinten, H. Schwarz, T.W. Pearson, and P. Overath Synchronous differentiation of Trypanosoma brucei from bloodstream to procyclic forms in vitro Eur J Biochem 192 2 1990 373 378
100. S.Z. Shapiro, J. Naessen, and B. Liesegang Analysis by flow cytometry of DNA synthesis during the life cycle of African trypanosomes Acta Trop 41 4 1984 313 323
101. K.R. Matthews, and K. Gull Evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of African trypanosomes J Cell Biol 125 5 1994 1147 1156
102. E. Vassella, J.V. Den Abbeele, P. Butikofer, C.K. Renggli, A. Furger, and R. Brun A major surface glycoprotein of trypanosoma brucei is expressed transiently during development and can be regulated post-transcriptionally by glycerol or hypoxia Genes Dev 14 5 2000 615 626
103. A. Acosta-Serrano, E. Vassella, M. Liniger, C. Kunz Renggli, R. Brun, and I. Roditi The surface coat of procyclic Trypanosoma brucei: programmed expression and proteolytic cleavage of procyclin in the tsetse fly Proc Natl Acad Sci U S A 98 4 2001 1513 1518
104. E. Vassella, A. Acosta-Serrano, E. Studer, S.H. Lee, P.T. Englund, and I. Roditi Multiple procyclin isoforms are expressed differentially during the development of insect forms of Trypanosoma brucei J Mol Biol 312 4 2001 597 607
105. I. Roditi, and M. Liniger Dressed for success: the surface coats of insect-borne protozoan parasites Trends Microbiol 10 3 2002 128 134
106. E. Vassella, B. Reuner, B. Yutzy, and M. Boshart Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway J Cell Sci 110 Pt 21 1997 2661 2671
107. B.M. Mony, P. MacGregor, A. Ivens, F. Rojas, A. Cowton, and J. Young Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei Nature 505 7485 2014 681 685
108. S. Dean, R. Marchetti, K. Kirk, and K.R. Matthews A surface transporter family conveys the trypanosome differentiation signal Nature 459 7244 2009 213 217
109. M. Engstler, and M. Boshart Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in Trypanosoma brucei Genes Dev 18 22 2004 2798 2811
110. B. Szoor, J. Wilson, H. McElhinney, L. Tabernero, and K.R. Matthews Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes J Cell Biol 175 2 2006 293 303
111. B. Szoor, I. Ruberto, R. Burchmore, and K. Matthews A novel phosphatase cascade reglates differentiation in trypanosomes via a glycosomal signaling pathway Genes Dev 24 2010 1306 1316
112. B. Szoor, N.A. Dyer, I. Ruberto, A. Acosta-Serrano, and K.R. Matthews Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei PLoS Pathog 9 10 2013 e1003689
113. J. Van Den Abbeele, Y. Claes, D. van Bockstaele, D. Le Ray, and M. Coosemans Trypanosoma brucei spp. development in the tsetse fly: characterization of the post-mesocyclic stages in the foregut and proboscis Parasitology 118 Pt 5 1999 469 478
114. R. Sharma, L. Peacock, E. Gluenz, K. Gull, W. Gibson, and M. Carrington Asymmetric cell division as a route to reduction in cell length and change in cell morphology in trypanosomes Protist 159 1 2008 137 151
115. M. Oberle, O. Balmer, R. Brun, and I. Roditi Bottlenecks and the maintenance of minor genotypes during the life cycle of Trypanosoma brucei PLoS Pathog 6 7 2010 e1001023
116. L. Peacock, V. Ferris, R. Sharma, J. Sunter, M. Bailey, and M. Carrington Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly Proc Natl Acad Sci U S A 108 9 2011 3671 3676
117. L. Peacock, M. Bailey, M. Carrington, and W. Gibson Meiosis and haploid gametes in the pathogen Trypanosoma brucei Curr Biol 24 2 2014 181 186
118. N.G. Kolev, K. Ramey-Butler, G.A. Cross, E. Ullu, and C. Tschudi Developmental progression to infectivity in Trypanosoma brucei triggered by an RNA-binding protein Science 338 6112 2012 1352 1353
119. I. Subota, B. Rotureau, T. Blisnick, S. Ngwabyt, M. Durand-Dubief, and M. Engstler ALBA proteins are stage regulated during trypanosome development in the tsetse fly and participate in differentiation Mol Biol Cell 22 22 2011 4205 4219
120. P. Hayes, V. Varga, S. Olego-Fernandez, J. Sunter, M.L. Ginger, and K. Gull Modulation of a cytoskeletal calpain-like protein induces major transitions in trypanosome morphology J Cell Biol 206 3 2014 377 384
121. S. Kramer, R. Queiroz, L. Ellis, J.D. Hoheisel, C. Clayton, and M. Carrington The RNA helicase DHH1 is central to the correct expression of many developmentally regulated mRNAs in trypanosomes J Cell Sci 123 Pt 5 2010 699 711
122. C. Tschudi, and E. Ullu Polygene transcripts are precursors to calmodulin mRNAs in trypanosomes EMBO J 7 2 1988 455 463
123. S. Martinez-Calvillo, S. Yan, D. Nguyen, M. Fox, K. Stuart, and P.J. Myler Transcription of Leishmania major Friedlin chromosome 1 initiates in both directions within a single region Mol Cell 11 5 2003 1291 1299
124. T.N. Siegel, D.R. Hekstra, L.E. Kemp, L.M. Figueiredo, J.E. Lowell, and D. Fenyo Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei Genes Dev 23 9 2009 1063 1076
125. B. Schimanski, T.N. Nguyen, and A. Gunzl Characterization of a multisubunit transcription factor complex essential for spliced-leader RNA gene transcription in Trypanosoma brucei Mol Cell Biol 25 16 2005 7303 7313
126. A. Das, Q. Zhang, J.B. Palenchar, B. Chatterjee, G.A. Cross, and V. Bellofatto Trypanosomal TBP functions with the multisubunit transcription factor tSNAP to direct spliced-leader RNA gene expression Mol Cell Biol 25 16 2005 7314 7322
127. B.S. Ibrahim, N. Kanneganti, G.E. Rieckhof, A. Das, D.V. Laurents, and J.B. Palenchar Structure of the C-terminal domain of transcription factor IIB from Trypanosoma brucei Proc Natl Acad Sci U S A 106 32 2009 13242 13247
128. K.R. Matthews, C. Tschudi, and E. Ullu A common pyrimidine-rich motif governs trans-splicing and polyadenylation of tubulin polycistronic pre-mRNA in trypanosomes Genes Dev 8 4 1994 491 501
129. G. Mair, H. Shi, H. Li, A. Djikeng, H.O. Aviles, and J.R. Bishop A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA RNA 6 2 2000 163 169
130. D. Nilsson, K. Gunasekera, J. Mani, M. Osteras, L. Farinelli, and L. Baerlocher Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei PLoS Pathog 6 8 2010 e1001037
131. T.N. Siegel, D.R. Hekstra, X. Wang, S. Dewell, and G.A. Cross Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites Nucleic Acids Res 38 15 2010 4946 4957
132. H.G. van Luenen, C. Farris, S. Jan, P.A. Genest, P. Tripathi, and A. Velds Glucosylated hydroxymethyluracil: DNA Base J, prevents transcriptional readthrough in Leishmania Cell 150 5 2012 909 921
133. L.J. Cliffe, T.N. Siegel, M. Marshall, G.A. Cross, and R. Sabatini Two thymidine hydroxylases differentially regulate the formation of glucosylated DNA at regions flanking polymerase II polycistronic transcription units throughout the genome of Trypanosoma brucei Nucleic Acids Res 38 12 2010 3923 3935
134. A. Furger, N. Schurch, U. Kurath, and I. Roditi Elements in the 3′ untranslated region of procyclin mRNA regulate expression in insect forms of Trypanosoma brucei by modulating RNA stability and translation Mol Cell Biol 17 8 1997 4372 4380
135. N.G. Kolev, E. Ullu, and C. Tschudi The emerging role of RNA-binding proteins in the life cycle of Trypanosoma brucei Cell Microbiol 16 4 2014 482 489
136. J. Mani, A. Guttinger, B. Schimanski, M. Heller, A. Acosta-Serrano, and P. Pescher Alba-domain proteins of Trypanosoma brucei are cytoplasmic RNA-binding proteins that interact with the translation machinery PLoS ONE 6 7 2011 e22463
137. P. Walrad, A. Paterou, A. Acosta Serrano, and MK Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements PLoS Pathog 5 2009 e1000317
138. A.M. Estevez The RNA-binding protein TbDRBD3 regulates the stability of a specific subset of mRNAs in trypanosomes Nucleic Acids Res 36 14 2008 4573 4586
139. S.M. Fernandez-Moya, M. Carrington, and A.M. Estevez A short RNA stem-loop is necessary and sufficient for repression of gene expression during early logarithmic phase in trypanosomes Nucleic Acids Res 42 11 2014 7201 7209
140. C.E. Clayton Networks of gene expression regulation in Trypanosoma brucei Mol Biochem Parasitol 195 2 2014 96 106
141. C. Clayton, and M. Shapira Post-transcriptional regulation of gene expression in trypanosomes and leishmanias Mol Biochem Parasitol 156 2 2007 93 101
142. T.N. Siegel, K. Gunasekera, G.A. Cross, and T. Ochsenreiter Gene expression in Trypanosoma brucei: lessons from high-throughput RNA sequencing Trends Parasitol 27 10 2011 434 441
143. M.D. Urbaniak, D.M. Martin, and M.A. Ferguson Global quantitative SILAC phosphoproteomics reveals differential phosphorylation is widespread between the procyclic and bloodstream form lifecycle stages of Trypanosoma brucei J Proteome Res 12 5 2013 2233 2244
144. K. Gunasekera, D. Wuthrich, S. Braga-Lagache, M. Heller, and T. Ochsenreiter Proteome remodelling during development from blood to insect-form Trypanosoma brucei quantified by SILAC and mass spectrometry BMC Genomics 13 1 2012 556
145. J.J. Vasquez, C.C. Hon, J.T. Vanselow, A. Schlosser, and T.N. Siegel Comparative ribosome profiling reveals extensive translational complexity in different Trypanosoma brucei life cycle stages Nucleic Acids Res 42 6 2014 3623 3637
146. M. Ericson, M.A. Janes, F. Butter, M. Mann, E. Ullu, and C. Tschudi On the extent and role of the small proteome in the parasitic eukaryote Trypanosoma brucei BMC Biol 12 2014 14
147. B.M. Bakker, P.A.M. Michels, F.R. Opperdoes, and H.V. Westerhoff Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes J Biol Chem 272 6 1997 3207 3215
148. B.M. Bakker, M.C. Walsh, B.H. ter Kuile, F.I. Mensonides, P.A. Michels, and F.R. Opperdoes Contribution of glucose transport to the control of the glycolytic flux in Trypanosoma brucei Proc Natl Acad Sci U S A 96 18 1999 10098 10103
149. B.M. Bakker, F.I. Mensonides, B. Teusink, P. van Hoek, P.A. Michels, and H.V. Westerhoff Compartmentation protects trypanosomes from the dangerous design of glycolysis Proc Natl Acad Sci U S A 97 5 2000 2087 2092
150. M.P. Barrett, B.M. Bakker, and R. Breitling Metabolomic systems biology of trypanosomes Parasitology 137 9 2010 1285 1290
151. A.G. Tielens, and J.J. van Hellemond Surprising variety in energy metabolism within Trypanosomatidae Trends Parasitol 25 10 2009 482 490
152. F. Bringaud, L. Riviere, and V. Coustou Energy metabolism of trypanosomatids: adaptation to available carbon sources Mol Biochem Parasitol 149 1 2006 1 9
153. M. Mazet, P. Morand, M. Biran, G. Bouyssou, P. Courtois, and S. Daulouede Revisiting the central metabolism of the bloodstream forms of Trypanosoma brucei: production of acetate in the mitochondrion is essential for parasite viability PLoS Negl Trop Dis 7 12 2013 e2587
154. T.K. Smith, and P. Butikofer Lipid metabolism in Trypanosoma brucei Mol Biochem Parasitol 172 2 2010 66 79
155. S.H. Lee, J.L. Stephens, K.S. Paul, and P.T. Englund Fatty acid synthesis by elongases in trypanosomes Cell 126 4 2006 691 699
156. N.R. Sturm, and L. Simpson Kinetoplast DNA minicircles encode guide RNAs for editing of cytochrome oxidase subunit III mRNA Cell 61 5 1990 879 884
157. B. Blum, N. Bakalara, and L. Simpson A model for RNA editing in kinetoplastid mitochondria: guide RNA molecules transcribed from maxicircle DNA provide the edited information Cell 60 2 1990 189 198
158. H.U. Goringer 'Gestalt,' composition and function of the Trypanosoma brucei editosome Annu Rev Microbiol 66 2012 65 82
159. A. Schnaufer, A.K. Panigrahi, B. Panicucci, R.P. Igo Jr., E. Wirtz, and R. Salavati An RNA ligase essential for RNA editing and survival of the bloodstream form of Trypanosoma brucei Science 291 5511 2001 2159 2162
160. R. Aphasizhev, and I. Aphasizheva Emerging roles of PPR proteins in trypanosomes: switches, blocks, and triggers RNA Biol 10 9 2013 1495 1500
161. M.W. Gray, J. Lukes, J.M. Archibald, P.J. Keeling, and W.F. Doolittle Cell biology, Irremediable complexity? Science 330 6006 2010 920 921
162. D. Speijer Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity Bioessays 33 5 2011 344 349
163. A.L. ten Asbroek, M. Ouellette, and P. Borst Targeted insertion of the neomycin phosphotransferase gene into the tubulin gene cluster of Trypanosoma brucei Nature 348 6297 1990 174 175
164. J. Eid, and B. SollnerWebb Stable integrative transformation of Trypanosoma brucei that occurs exclusively by homologous recombination Proc Natl Acad Sci U S A 88 6 1991 2118 2121
165. E. Wirtz, and C. Clayton Inducible gene expression in trypanosomes mediated by a prokaryotic repressor Science 268 5214 1995 1179 1183
166. E. Wirtz, C. Hartmann, and C. Clayton Gene expression mediated by bacteriophage T3 and T7 RNA polymerases in transgenic trypanosomes Nucleic Acids Res 22 19 1994 3887 3894
167. E. Wirtz, M. Hoek, and G.A. Cross Regulated processive transcription of chromatin by T7 RNA polymerase in Trypanosoma brucei Nucleic Acids Res 26 20 1998 4626 4634
168. H. Ngo, C. Tschudi, K. Gull, and E. Ullu Double-stranded RNA induces mRNA degradation in Trypanosoma brucei Proc Natl Acad Sci U S A 95 25 1998 14687 14692
169. Z. Wang, J.C. Morris, M.E. Drew, and P.T. Englund Inhibition of Trypanosoma brucei gene expression by RNA interference using an integratable vector with opposing T7 promoters J Biol Chem 275 51 2000 40174 40179
170. D.J. LaCount, S. Bruse, K.L. Hill, and J.E. Donelson Double-stranded RNA interference in Trypanosoma brucei using head-to-head promoters Mol Biochem Parasitol 111 1 2000 67 76
171. Z. Wang, and P.T. Englund RNA interference of a trypanosome topoisomerase II causes progressive loss of mitochondrial DNA EMBO J 20 17 2001 4674 4683
172. H. Shi, A. Djikeng, T. Mark, E. Wirtz, C. Tschudi, and E. Ullu Genetic interference in Trypanosoma brucei by heritable and inducible double-stranded RNA RNA 6 7 2000 1069 1076
173. N.G. Kolev, C. Tschudi, and E. Ullu RNA interference in protozoan parasites: achievements and challenges Eukaryot Cell 10 9 2011 1156 1163
174. J.C. Morris, Z. Wang, M.E. Drew, and P.T. Englund Glycolysis modulates trypanosome glycoprotein expression as revealed by an RNAi library EMBO J 21 17 2002 4429 4438
175. G. Burkard, C.M. Fragoso, and I. Roditi Highly efficient stable transformation of bloodstream forms of Trypanosoma brucei Mol Biochem Parasitol 153 2 2007 220 223
176. S. Alsford, and D. Horn Single-locus targeting constructs for reliable regulated RNAi and transgene expression in Trypanosoma brucei Mol Biochem Parasitol 161 1 2008 76 79
177. S. Alsford, T. Kawahara, L. Glover, and D. Horn Tagging a T. Brucei RRNA locus improves stable transfection efficiency and circumvents inducible expression position effects Mol Biochem Parasitol 144 2 2005 142 148
178. L. Glover, and D. Horn Site-specific DNA double-strand breaks greatly increase stable transformation efficiency in Trypanosoma brucei Mol Biochem Parasitol 166 2 2009 194 197
179. N. Baker, S. Alsford, and D. Horn Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6 Mol Biochem Parasitol 176 1 2011 55 57
180. G. Schumann Burkard, P. Jutzi, and I. Roditi Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters Mol Biochem Parasitol 175 1 2011 91 94
181. S. Alsford, D.J. Turner, S.O. Obado, A. Sanchez-Flores, L. Glover, and M. Berriman High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 21 6 2011 915 924
182. S. Alsford, S. Eckert, N. Baker, L. Glover, A. Sanchez-Flores, and K.F. Leung High-throughput decoding of antitrypanosomal drug efficacy and resistance Nature 482 7384 2012 232 236
183. G. Priotto, S. Kasparian, W. Mutombo, D. Ngouama, S. Ghorashian, and U. Arnold Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial Lancet 374 9683 2009 56 64
184. J.A. Frearson, S. Brand, S.P. McElroy, L.A. Cleghorn, O. Smid, and L. Stojanovski N-myristoyltransferase inhibitors as new leads to treat sleeping sickness Nature 464 7289 2010 728 732
185. I.H. Gilbert Drug discovery for neglected diseases: molecular target-based and phenotypic approaches J Med Chem 56 20 2013 7719 7726
186. P. Maser, S. Wittlin, M. Rottmann, T. Wenzler, M. Kaiser, and R. Brun Antiparasitic agents: new drugs on the horizon Curr Opin Pharmacol 12 5 2012 562 566
187. M. Iten, H. Mett, A. Evans, J.C. Enyaru, R. Brun, and R. Kaminsky Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to d,l-alpha-difluoromethylornithine Antimicrob Agents Chemother 41 9 1997 1922 1925
188. A. Roy Chowdhury, R. Bakshi, J. Wang, G. Yildirir, B. Liu, and V. Pappas-Brown The killing of African trypanosomes by ethidium bromide PLoS Pathog 6 12 2010 e1001226
189. R.J. Wheeler The trypanolytic factor-mechanism: impacts and applications Trends Parasitol 26 9 2010 457 464
190. P. MacGregor, A. Ivens, S. Shave, I. Collie, D. Gray, and M. Auer High-throughput chemical screening for antivirulence developmental phenotypes in Trypanosoma brucei Eukaryot Cell 13 3 2014 412 426
191. C.W. Duffy, L. MacLean, L. Sweeney, A. Cooper, C.M. Turner, and A. Tait Population genetics of Trypanosoma brucei rhodesiense: clonality and diversity within and between foci PLoS Negl Trop Dis 7 11 2013 e2526
192. A. MacLeod, A. Tait, and C.M. Turner The population genetics of Trypanosoma brucei and the origin of human infectivity Philos Trans R Soc Lond B: Biol Sci 356 1411 2001 1035 1044
193. I. Goodhead, P. Capewell, J.W. Bailey, T. Beament, M. Chance, and S. Kay Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence MBio 4 4 2013
194. M. Oberholzer, M.A. Lopez, B.T. McLelland, and K.L. Hill Social motility in African trypanosomes PLoS Pathog 6 1 2010 e1000739
195. M.A. Lopez, H.T. Nguyen, M. Oberholzer, and K.L. Hill Social parasites Curr Opin Microbiol 14 6 2011 642 648
196. P. MacGregor, B. Szoor, N.J. Savill, and K.R. Matthews Trypanosomal immune evasion, chronicity and transmission: an elegant balancing act Nat Rev Microbiol 10 6 2012 431 438