1932

Abstract

African trypanosomes are responsible for important diseases of humans and animals in sub-Saharan Africa. The best-studied species is , which is characterized by development in the mammalian host between morphologically slender and stumpy forms. The latter are adapted for transmission by the parasite's vector, the tsetse fly. The development of stumpy forms is driven by density-dependent quorum sensing (QS), the molecular basis for which is now coming to light. In this review, I discuss the historical context and biological features of trypanosome QS and how it contributes to the parasite's infection dynamics within its mammalian host. Also, I discuss how QS can be lost in different trypanosome species, such as and , or modulated when parasites find themselves competing with others of different genotypes or of different trypanosome species in the same host. Finally, I consider the potential to exploit trypanosome QS therapeutically.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-020321-115246
2021-10-08
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/micro/75/1/annurev-micro-020321-115246.html?itemId=/content/journals/10.1146/annurev-micro-020321-115246&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Abbas AH, Silva Pereira S, D'Archivio S, Wickstead B, Morrison LJ et al. 2018. The structure of a conserved telomeric region associated with variant antigen loci in the blood parasite Trypanosoma congolense. Genome Biol. Evol. 10:2458–73
    [Google Scholar]
  2. 2. 
    Aregawi WG, Agga GE, Abdi RD, Buscher P. 2019. Systematic review and meta-analysis on the global distribution, host range, and prevalence of Trypanosoma evansi. Parasites Vectors 12:67
    [Google Scholar]
  3. 3. 
    Baker JR, Robertson DH. 1957. An experiment on the infectivity to Glossina morsitans of a strain of Trypanosoma rhodesiense and of a strain of T. brucei, with some observations on the longevity of infected flies. Ann. Trop. Med. Parasitol. 51:121–35
    [Google Scholar]
  4. 4. 
    Balber AE. 1972. Trypanosoma brucei: fluxes of the morphological variants in intact and X-irradiated mice. Exp. Parasitol. 31:307–19
    [Google Scholar]
  5. 5. 
    Banks KL. 1978. Binding of Trypanosoma congolense to the walls of small blood vessels. J. Protozool. 25:241–45
    [Google Scholar]
  6. 6. 
    Banks KL. 1979. In vitro binding of Trypanosoma congolense to erythrocytes. J. Protozool. 26:103–8
    [Google Scholar]
  7. 7. 
    Barquilla A, Saldivia M, Diaz R, Bart JM, Vidal I et al. 2012. Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei. PNAS 109:14399–404
    [Google Scholar]
  8. 8. 
    Barry JD. 1986. Antigenic variation during Trypanosoma vivax infections of different host species. Parasitology 92:Pt 151–65
    [Google Scholar]
  9. 9. 
    Barry JD, McCulloch R. 2001. Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Adv. Parasitol. 49:1–70
    [Google Scholar]
  10. 10. 
    Bastos IM, Motta FN, Charneau S, Santana JM, Dubost L et al. 2010. Prolyl oligopeptidase of Trypanosoma brucei hydrolyzes native collagen, peptide hormones and is active in the plasma of infected mice. Microbes Infect 12:457–66
    [Google Scholar]
  11. 11. 
    Batram C, Jones NG, Janzen CJ, Markert SM, Engstler M 2014. Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei. eLife 3:e02324
    [Google Scholar]
  12. 12. 
    Bellmann-Sickert K, Beck-Sickinger AG. 2010. Peptide drugs to target G protein-coupled receptors. Trends Pharmacol. Sci. 31:434–41
    [Google Scholar]
  13. 13. 
    Benz C, Dondelinger F, McKean PG, Urbaniak MD. 2017. Cell cycle synchronisation of Trypanosoma brucei by centrifugal counter-flow elutriation reveals the timing of nuclear and kinetoplast DNA replication. Sci. Rep. 7:17599
    [Google Scholar]
  14. 14. 
    Berberof M, Perez-Morga D, Pays E. 2001. A receptor-like flagellar pocket glycoprotein specific to Trypanosoma brucei gambiense. Mol. Biochem. Parasitol. 113:127–38
    [Google Scholar]
  15. 15. 
    Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H et al. 2005. The genome of the African trypanosome Trypanosoma brucei. Science 309:416–22
    [Google Scholar]
  16. 16. 
    Bradford W, Buckholz A, Morton J, Price C, Jones AM, Urano D. 2013. Eukaryotic G protein signaling evolved to require G protein-coupled receptors for activation. Sci. Signal. 6:ra37
    [Google Scholar]
  17. 17. 
    Brown SP, Buckling A. 2008. A social life for discerning microbes. Cell 135:600–3
    [Google Scholar]
  18. 18. 
    Brown SP, Taddei F. 2007. The durability of public goods changes the dynamics and nature of social dilemmas. PLOS ONE 2:e593
    [Google Scholar]
  19. 19. 
    Brown SP, West SA, Diggle SP, Griffin AS. 2009. Social evolution in micro-organisms and a Trojan horse approach to medical intervention strategies. Philos. Trans. R. Soc. Lond. B 364:3157–68
    [Google Scholar]
  20. 20. 
    Bruce D, Harvey D, Hamerton A, Davey J, Bruce L. 1912. The morphology of the trypanosome causing disease in man in Nyasaland. Proc. R. Soc. B 85:423–33
    [Google Scholar]
  21. 21. 
    Brun R, Hecker H, Lun ZR. 1998. Trypanosoma evansi and T. equiperdum: distribution, biology, treatment and phylogenetic relationship (a review). Vet. Parasitol. 79:95–107
    [Google Scholar]
  22. 22. 
    Buscher P, Gonzatti MI, Hebert L, Inoue N, Pascucci I et al. 2019. Equine trypanosomosis: enigmas and diagnostic challenges. Parasites Vectors 12:234
    [Google Scholar]
  23. 23. 
    Caljon G, Van Reet N, De Trez C, Vermeersch M, Perez-Morga D, Van Den Abbeele J. 2016. The dermis as a delivery site of Trypanosoma brucei for tsetse flies. PLOS Pathog 12:e1005744
    [Google Scholar]
  24. 24. 
    Capewell P, Atkins K, Weir W, Jamonneau V, Camara M et al. 2019. Resolving the apparent transmission paradox of African sleeping sickness. PLOS Biol 17:e3000105
    [Google Scholar]
  25. 25. 
    Capewell P, Clucas C, DeJesus E, Kieft R, Hajduk S et al. 2013. The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. PLOS Pathog 9:e1003686
    [Google Scholar]
  26. 26. 
    Capewell P, Cren-Travaille C, Marchesi F, Johnston P, Clucas C et al. 2016. The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes. eLife 5:e17716
    [Google Scholar]
  27. 27. 
    Carnes J, Anupama A, Balmer O, Jackson A, Lewis M et al. 2015. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty. PLOS Negl. Trop. Dis. 9:e3404
    [Google Scholar]
  28. 28. 
    Cayla M, McDonald L, MacGregor P, Matthews K 2020. An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei. eLife 9:e51620
    [Google Scholar]
  29. 29. 
    Corson JF. 1936. Experimental transmission of Trypanosoma gambiense by Glossina morsitans through monkeys. Ann. Trop. Med. Parasitol. 30:389–400
    [Google Scholar]
  30. 30. 
    Dean S, Gould MK, Dewar CE, Schnaufer AC 2013. Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. PNAS 110:14741–46
    [Google Scholar]
  31. 31. 
    Dean S, Marchetti R, Kirk K, Matthews KR. 2009. A surface transporter family conveys the trypanosome differentiation signal. Nature 459:213–17
    [Google Scholar]
  32. 32. 
    Deitsch KW, Lukehart SA, Stringer JR. 2009. Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat. Rev. Microbiol. 7:493–503
    [Google Scholar]
  33. 33. 
    Desquesnes M, Biteau-Coroller F, Bouyer J, Dia ML, Foil L. 2009. Development of a mathematical model for mechanical transmission of trypanosomes and other pathogens of cattle transmitted by tabanids. Int. J. Parasitol. 39:333–46
    [Google Scholar]
  34. 34. 
    Dewar CE, MacGregor P, Cooper S, Gould MK, Matthews KR et al. 2018. Mitochondrial DNA is critical for longevity and metabolism of transmission stage Trypanosoma brucei. PLOS Pathog 14:e1007195
    [Google Scholar]
  35. 35. 
    Domenicali Pfister D, Burkard G, Morand S, Renggli CK, Roditi I, Vassella E 2006. A mitogen-activated protein kinase controls differentiation of bloodstream forms of Trypanosoma brucei. Eukaryot. Cell 5:1126–35
    [Google Scholar]
  36. 36. 
    Emge P, Moeller J, Jang H, Rusconi R, Yawata Y et al. 2016. Resilience of bacterial quorum sensing against fluid flow. Sci. Rep. 6:33115
    [Google Scholar]
  37. 37. 
    Engstler M, Pfohl P, Herminghaus S, Boshart M, Wiegerttjes G et al. 2007. Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131:505–15
    [Google Scholar]
  38. 38. 
    Erben ED, Fadda A, Lueong S, Hoheisel JD, Clayton C. 2014. A genome-wide tethering screen reveals novel potential post-transcriptional regulators in Trypanosoma brucei. PLOS Pathog 10:e1004178
    [Google Scholar]
  39. 39. 
    Giordani F, Morrison LJ, Rowan TG, Koning HPDE, Barrett MP. 2016. The animal trypanosomiases and their chemotherapy: a review. Parasitology 143:1862–89
    [Google Scholar]
  40. 40. 
    Gunzl A, Kirkham JK, Nguyen TN, Badjatia N, Park SH. 2015. Mono-allelic VSG expression by RNA polymerase I in Trypanosoma brucei: expression site control from both ends?. Gene 556:68–73
    [Google Scholar]
  41. 41. 
    Hill KL. 2003. Biology and mechanism of trypanosome cell motility. Eukaryot. Cell 2:200–8
    [Google Scholar]
  42. 42. 
    Hovel-Miner G, Mugnier M, Papavasiliou FN, Pinger J, Schulz D. 2015. A host-pathogen interaction reduced to first principles: antigenic variation in T. brucei. Results Probl. Cell Differ 57:23–46
    [Google Scholar]
  43. 43. 
    Imhof S, Roditi I. 2015. The social life of African trypanosomes. Trends Parasitol 31:490–98
    [Google Scholar]
  44. 44. 
    Jackson AP, Berry A, Aslett M, Allison HC, Burton P et al. 2012. Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species. PNAS 109:3416–21
    [Google Scholar]
  45. 45. 
    Kamidi CM, Saarman NP, Dion K, Mireji PO, Ouma C et al. 2017. Multiple evolutionary origins of Trypanosoma evansi in Kenya. PLOS Negl. Trop. Dis. 11:e0005895
    [Google Scholar]
  46. 46. 
    Kennedy PGE. 2019. Update on human African trypanosomiasis (sleeping sickness). J. Neurol. 266:2334–37
    [Google Scholar]
  47. 47. 
    Kolev NG, Ramey-Butler K, Cross GA, Ullu E, Tschudi C. 2012. Developmental progression to infectivity in Trypanosoma brucei triggered by an RNA-binding protein. Science 338:1352–53
    [Google Scholar]
  48. 48. 
    Laxman S, Riechers A, Sadilek M, Schwede F, Beavo JA 2006. Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms. PNAS 103:19194–99
    [Google Scholar]
  49. 49. 
    Lord JS, Hargrove JW, Torr SJ, Vale GA. 2018. Climate change and African trypanosomiasis vector populations in Zimbabwe's Zambezi Valley: a mathematical modelling study. PLOS Med 15:e1002675
    [Google Scholar]
  50. 50. 
    Lythgoe KA, Morrison LJ, Read AF, Barry JD 2007. Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation. PNAS 104:8095–100
    [Google Scholar]
  51. 51. 
    MacGregor P, Matthews KR. 2012. Identification of the regulatory elements controlling the transmission stage-specific gene expression of PAD1 in Trypanosoma brucei. Nucleic Acids Res 40:7705–17
    [Google Scholar]
  52. 52. 
    MacGregor P, Savill NJ, Hall D, Matthews KR. 2011. Transmission stages dominate trypanosome within-host dynamics during chronic infections. Cell Host Microbe 9:310–18
    [Google Scholar]
  53. 53. 
    MacGregor P, Szoor B, Savill NJ, Matthews KR. 2012. Trypanosomal immune evasion, chronicity and transmission: an elegant balancing act. Nat. Rev. Microbiol. 10:431–38
    [Google Scholar]
  54. 54. 
    Macleod OJS, Bart JM, MacGregor P, Peacock L, Savill NJ et al. 2020. A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies. Nat. Commun. 11:1326
    [Google Scholar]
  55. 55. 
    Magez S, Pinto Torres JE, Obishakin E, Radwanska M 2020. Infections with extracellular trypanosomes require control by efficient innate immune mechanisms and can result in the destruction of the mammalian humoral immune system. Front. Immunol. 11:382
    [Google Scholar]
  56. 56. 
    Magez S, Schwegmann A, Atkinson R, Claes F, Drennan M et al. 2008. The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice. PLOS Pathog 4:e1000122
    [Google Scholar]
  57. 57. 
    Magez S, Truyens C, Merimi M, Radwanska M, Stijlemans B et al. 2004. P75 tumor necrosis factor-receptor shedding occurs as a protective host response during African trypanosomiasis. J. Infect. Dis. 189:527–39
    [Google Scholar]
  58. 58. 
    Marcello L, Barry JD 2007. 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 17:1344–52
    [Google Scholar]
  59. 59. 
    Matthews KR, Gull K. 1994. Evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of African trypanosomes. J. Cell Biol. 125:1147–56
    [Google Scholar]
  60. 60. 
    McCulloch R, Cobbold CA, Figueiredo L, Jackson A, Morrison LJ et al. 2017. Emerging challenges in understanding trypanosome antigenic variation. Emerg. Top. Life Sci. 1:585–92
    [Google Scholar]
  61. 61. 
    McDonald L, Cayla M, Ivens A, Mony BM, MacGregor P et al. 2018. Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes. PLOS Pathog 14:e1007145
    [Google Scholar]
  62. 62. 
    McLintock LM, Turner CM, Vickerman K. 1993. Comparison of the effects of immune killing mechanisms on Trypanosoma brucei parasites of slender and stumpy morphology. Parasite Immunol 15:475–80
    [Google Scholar]
  63. 63. 
    Mony BM, MacGregor P, Ivens A, Rojas F, Cowton A et al. 2014. Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei. Nature 505:681–85
    [Google Scholar]
  64. 64. 
    Morrison LJ, Marcello L, McCulloch R 2009. Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity. Cell Microbiol 11:1724–34
    [Google Scholar]
  65. 65. 
    Morrison LJ, Vezza L, Rowan T, Hope JC. 2016. Animal African trypanosomiasis: time to increase focus on clinically relevant parasite and host species. Trends Parasitol 32:599–607
    [Google Scholar]
  66. 66. 
    Morty RE, Lonsdale-Eccles JD, Mentele R, Auerswald EA, Coetzer TH. 2001. Trypanosome-derived oligopeptidase B is released into the plasma of infected rodents, where it persists and retains full catalytic activity. Infect. Immun. 69:2757–61
    [Google Scholar]
  67. 67. 
    Moss CX, Brown E, Hamilton A, Van der Veken P, Augustyns K, Mottram JC. 2015. An essential signal peptide peptidase identified in an RNAi screen of serine peptidases of Trypanosoma brucei. PLOS ONE 10:e0123241
    [Google Scholar]
  68. 68. 
    Mugnier MR, Cross GA, Papavasiliou FN. 2015. The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science 347:1470–73
    [Google Scholar]
  69. 69. 
    Mukherjee S, Bassler BL. 2019. Bacterial quorum sensing in complex and dynamically changing environments. Nat. Rev. Microbiol. 17:371–82
    [Google Scholar]
  70. 70. 
    Nolan DP, Rolin S, Rodriguez JR, Van Den Abbeele J, Pays E. 2000. Slender and stumpy bloodstream forms of Trypanosoma brucei display a differential response to extracellular acidic and proteolytic stress. Eur. J. Biochem. 267:18–27
    [Google Scholar]
  71. 71. 
    Pandey S, Nelson DC, Assmann SM. 2009. Two novel GPCR-type G proteins are abscisic acid receptors in Arabidopsis. Cell 136:136–48
    [Google Scholar]
  72. 72. 
    Papenfort K, Bassler BL. 2016. Quorum sensing signal-response systems in Gram-negative bacteria. Nat. Rev. Microbiol. 14:576–88
    [Google Scholar]
  73. 73. 
    Qvit N, Rubin SJS, Urban TJ, Mochly-Rosen D, Gross ER. 2017. Peptidomimetic therapeutics: scientific approaches and opportunities. Drug Discov. Today 22:454–62
    [Google Scholar]
  74. 74. 
    Reuner B, Vassella E, Yutzy B, Boshart M. 1997. Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture. Mol. Biochem. Parasitol. 90:269–80
    [Google Scholar]
  75. 75. 
    Rico E, Ivens A, Glover L, Horn D, Matthews KR. 2017. Genome-wide RNAi selection identifies a regulator of transmission stage-enriched gene families and cell-type differentiation in Trypanosoma brucei. PLOS Pathog 13:e1006279
    [Google Scholar]
  76. 76. 
    Robertson M. 1912. Notes on the polymorphism of Trypanosoma gambiense in the blood and its relation to the exogenous cycle in Glossina palpalis. Proc. R. Soc. B 85:241–539
    [Google Scholar]
  77. 77. 
    Rojas F, Silvester E, Young J, Milne R, Tettey M et al. 2018. Oligopeptide signaling through TbGPR89 drives trypanosome quorum sensing. Cell 176:306–17.e16
    [Google Scholar]
  78. 78. 
    Rotureau B, Van Den Abbeele J. 2013. Through the dark continent: African trypanosome development in the tsetse fly. Front. Cell Infect. Microbiol. 3:53
    [Google Scholar]
  79. 79. 
    Saada EA, DeMarco SF, Shimogawa MM, Hill KL. 2015.. “ With a Little Help from My Friends”—social motility in Trypanosoma brucei. PLOS Pathog 11:e1005272
    [Google Scholar]
  80. 80. 
    Saldivia M, Ceballos-Perez G, Bart JM, Navarro M. 2016. The AMPKα1 pathway positively regulates the developmental transition from proliferation to quiescence in Trypanosoma brucei. Cell Rep 17:660–70
    [Google Scholar]
  81. 81. 
    Schnaufer A, Domingo GJ, Stuart K. 2002. Natural and induced dyskinetoplastic trypanosomatids: how to live without mitochondrial DNA. Int. J. Parasitol. 32:1071–84
    [Google Scholar]
  82. 82. 
    Seed JR, Black SJ. 1997. A proposed density-dependent model of long slender to short stumpy transformation in the African trypanosomes. J. Parasitol. 83:656–62
    [Google Scholar]
  83. 83. 
    Seed JR, Sechelski J. 1988. Growth of pleomorphic Trypanosoma brucei rhodesiense in irradiated inbred mice. J. Parasitol. 74:781–89
    [Google Scholar]
  84. 84. 
    Seed JR, Sechelski JB. 1989. Mechanism of long slender (LS) to short stumpy (SS) transformation in the African trypanosomes. J. Protozool. 36:572–77
    [Google Scholar]
  85. 85. 
    Shapiro SZ, Naessen J, Liesegang B et al. 1984. Analysis by flow cytometry of DNA synthesis during the life cycle of African trypanosomes. Acta Trop 41:313–23
    [Google Scholar]
  86. 86. 
    Silva Pereira S, de Almeida Castilho Neto KJG, Duffy CW, Richards P, Noyes H et al. 2020. Variant antigen diversity in Trypanosoma vivax is not driven by recombination. Nat. Commun. 11:844
    [Google Scholar]
  87. 87. 
    Silva Pereira S, Trindade S, De Niz M, Figueiredo LM 2019. Tissue tropism in parasitic diseases. Open Biol. 9:190036 Erratum. 2019. Open Biol 9:6190124
    [Google Scholar]
  88. 88. 
    Silvester E, Ivens A, Matthews KR. 2018. A gene expression comparison of Trypanosoma brucei and Trypanosoma congolense in the bloodstream of the mammalian host reveals species-specific adaptations to density-dependent development. PLOS Negl. Trop. Dis. 12:e0006863
    [Google Scholar]
  89. 89. 
    Silvester E, Young J, Ivens A, Matthews KR. 2017. Interspecies quorum sensing in co-infections can manipulate trypanosome transmission potential. Nat. Microbiol. 2:111471–79
    [Google Scholar]
  90. 90. 
    Sima N, McLaughlin EJ, Hutchinson S, Glover L. 2019. Escaping the immune system by DNA repair and recombination in African trypanosomes. Open Biol. 9:190182
    [Google Scholar]
  91. 91. 
    Slamti L, Lereclus D. 2019. The oligopeptide ABC-importers are essential communication channels in Gram-positive bacteria. Res. Microbiol. 170:338–44
    [Google Scholar]
  92. 92. 
    Smith TK, Bringaud F, Nolan DP, Figueiredo LM. 2017. Metabolic reprogramming during the Trypanosoma brucei life cycle [version 2; peer review: 4 approved]. F1000Research 683 https://doi.org/10.12688/f1000research.10342.2
    [Crossref]
  93. 93. 
    Szoor B, Ruberto I, Burchmore R, Matthews K. 2010. A novel phosphatase cascade regulates differentiation in trypanosomes via a glycosomal signaling pathway. Genes Dev 24:1306–16
    [Google Scholar]
  94. 94. 
    Szoor B, Simon DV, Rojas F, Young J, Robinson DR et al. 2019. Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation. mBio 10:4e00875-19
    [Google Scholar]
  95. 95. 
    Szoor B, Wilson J, McElhinney H, Tabernero L, Matthews KR. 2006. Protein tyrosine phosphatase TbPTP1: a molecular switch controlling life cycle differentiation in trypanosomes. J. Cell Biol. 175:293–303
    [Google Scholar]
  96. 96. 
    Taddese B, Upton GJ, Bailey GR, Jordan SR, Abdulla NY et al. 2014. Do plants contain G protein-coupled receptors?. Plant Physiol. 164:287–307
    [Google Scholar]
  97. 97. 
    Trindade S, Rijo-Ferreira F, Carvalho T, Pinto-Neves D, Guegan F et al. 2016. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell Host Microbe 19:837–48
    [Google Scholar]
  98. 98. 
    Turner CM. 1990. The use of experimental artefacts in African trypanosome research. Parasitol. Today 6:14–17
    [Google Scholar]
  99. 99. 
    Tyler KM, Higgs PG, Matthews KR, Gull K. 2001. Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response. Proc. Biol. Sci. 268:2235–43
    [Google Scholar]
  100. 100. 
    Uzureau P, Uzureau S, Lecordier L, Fontaine F, Tebabi P et al. 2013. Mechanism of Trypanosoma brucei gambiense resistance to human serum. Nature 501:430–34
    [Google Scholar]
  101. 101. 
    Van Hoof LM. 1947. Observations on trypanosomiasis in the Belgian Congo. Trans. R. Soc. Trop. Med. Hyg. 40:728–61
    [Google Scholar]
  102. 102. 
    Vassella E, Boshart M. 1996. High molecular mass agarose matrix supports growth of bloodstream forms of pleomorphic Trypanosoma brucei strains in axenic culture. Mol. Biochem. Parasitol. 82:91–105
    [Google Scholar]
  103. 103. 
    Vassella E, Kramer R, Turner CM, Wankell M, Modes C et al. 2001. Deletion of a novel protein kinase with PX and FYVE-related domains increases the rate of differentiation of Trypanosoma brucei. Mol. Microbiol. 41:33–46
    [Google Scholar]
  104. 104. 
    Vassella E, Reuner B, Yutzy B, Boshart M. 1997. Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway. J. Cell Sci. 110:Part 212661–71
    [Google Scholar]
  105. 105. 
    Vickerman K. 1985. Developmental cycles and biology of pathogenic trypanosomes. Br. Med. Bull. 41:105–14
    [Google Scholar]
  106. 106. 
    Wheeler RJ. 2010. The trypanolytic factor—mechanism, impacts and applications. Trends Parasitol 26:457–64
    [Google Scholar]
  107. 107. 
    Wheeler RJ, Scheumann N, Wickstead B, Gull K, Vaughan S. 2013. Cytokinesis in Trypanosoma brucei differs between bloodstream and tsetse trypomastigote forms: implications for microtubule-based morphogenesis and mutant analysis. Mol. Microbiol. 90:1339–55
    [Google Scholar]
  108. 108. 
    Wijers DJ, Willett KC. 1960. Factors that may influence the infection rate of Glossina palpalis with Trypanosoma gambiense. II. The number and morphology of the trypanosomes present in the blood of the host at the time of the infected feed. Ann. Trop. Med. Parasitol. 54:341–50
    [Google Scholar]
  109. 109. 
    Williams P. 2002. Quorum sensing: an emerging target for antibacterial chemotherapy?. Expert Opin. Ther. Targets 6:257–74
    [Google Scholar]
  110. 110. 
    Xong HV, Vanhamme L, Chamekh M, Chimfwembe CE, Van Den Abbeele J et al. 1998. A VSG expression site–associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 95:839–46
    [Google Scholar]
  111. 111. 
    Ziegelbauer K, Quinten M, Schwarz H, Pearson TW, Overath P. 1990. Synchronous differentiation of Trypanosoma brucei from bloodstream to procyclic forms in vitro. Eur. J. Biochem. 192:373–78
    [Google Scholar]
  112. 112. 
    Zimmermann H, Subota I, Batram C, Kramer S, Janzen CJ et al. 2017. A quorum sensing-independent path to stumpy development in Trypanosoma brucei. PLOS Pathog 13:e1006324
    [Google Scholar]
/content/journals/10.1146/annurev-micro-020321-115246
Loading
/content/journals/10.1146/annurev-micro-020321-115246
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error