Acknowledgments

Work in our laboratory was supported by a grant from the U.S. National Institutes of Health (AI-107663).

References

  • 1. El-Sayed NM, Myler PJ, Bartholomeu DC, Nilsson D, Aggarwal G, Tran AN, et al. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 2005;309:409-15.
  • 2. Atwood III JA, Weatherly DB, Minning TA, Bundy B, Cavola C, Opperdoes FR, et al. The Trypanosoma cruzi proteome. Science 2005;309:473-6.
  • 3. Cordero EM, Nakayasu ES, Gentil LG, Yoshida N, Almeida IC, da Silveira JF. Proteomic analysis of detergent-solubilized membrane proteins from insect-developmental forms of Trypanosoma cruzi. J Proteome Res 2009;8:3642-52.
  • 4. Nakayasu ES, Gaynor MR, Sobreira TJ, Ross JA, Almeida IC. Phosphoproteomic analysis of the human pathogen Trypanosoma cruzi at the epimastigote stage. Proteomics 2009;9:3489-506.
  • 5. Sant’Anna C, Nakayasu ES, Pereira MG, Lourenco D, de Souza W, Almeida IC, et al. Subcellular proteomics of Trypanosoma cruzi reservosomes. Proteomics 2009;9: 1782- 94.
  • 6. Nakayasu ES, Yashunsky DV, Nohara LL, Torrecilhas AC, Nikolaev AV, Almeida IC. GPIomics: global analysis of glycosylphosphatidylinositol-anchored molecules of Trypanosoma cruzi. Mol Syst Biol 2009;5:261.
  • 7. Ferella M, Nilsson D, Darban H, Rodrigues C, Bontempi EJ, Docampo R, et al. Proteomics in Trypanosoma cruzi—localization of novel proteins to various organelles. Proteomics 2008;8:2735-49.
  • 8. Brunoro GV, Caminha MA, Ferreira AT, Leprevost Fda V, Carvalho PC, Perales J, et al. Reevaluating the Trypanosoma cruzi proteomic map: the shotgun description of bloodstream trypomastigotes. J Proteomics 2015;115:58-65.
  • 9. Queiroz RM, Charneau S, Mandacaru SC, Schwammle V, Lima BD, Roepstorff P, et al. Quantitative proteomic and phosphoproteomic analysis of Trypanosoma cruzi amastigo- genesis. Mol Cell Proteomics 2014;13:3457-72.
  • 10. de Godoy LM, Marchini FK, Pavoni DP, Rampazzo Rde C, Probst CM, Goldenberg S, et al. Quantitative proteomics of Trypanosoma cruzi during metacyclogenesis. Proteomics 2012;12:2694-703.
  • 11. Nakayasu ES, Sobreira TJ, Torres Jr. R, Ganiko L, Oliveira PS, Marques AF, et al. Improved proteomic approach for the discovery of potential vaccine targets in Trypanosoma cruzi. J Proteome Res 2012;11:237-46.
  • 12. Ulrich PN, Jimenez V, Park M, Martins VP, Atwood 3rd J, Moles K, et al. Identification of contractile vacuole proteins in Trypanosoma cruzi. PLoS ONE 2011;6:e18013.
  • 13. Bayer-Santos E, Aguilar-Bonavides C, Rodrigues SP, Cordero EM, Marques AF, Varela-Ramirez A, et al. Proteomic analysis of Trypanosoma cruzi secretome: characterization of two populations of extracellular vesicles and soluble proteins. J Proteome Res 2013;12:883-97.
  • 14. Brener Z. Present status of chemotherapy and chemoprophylaxis of human trypanosomiasis in the Western Hemisphere. Pharmacol Ther 1979;7:71-90.
  • 15. Docampo R, Moreno SN. Free radical metabolites in the mode of action of chemotherapeutic agents and phagocytic cells on Trypanosoma cruzi. Rev Infect Dis 1984;6: 223-38.
  • 16. Marr JJ, Docampo R. Chemotherapy for Chagas’ disease: a perspective of current therapy and considerations for future research. Rev Infect Dis 1986;8:884-903.
  • 17. Docampo R. Sensitivity of parasites to free radical damage by antiparasitic drugs. Chem Biol Interact 1990;73:1-27.
  • 18. Docampo R, Schmunis GA. Sterol biosynthesis inhibitors: potential chemotherapeutics against Chagas disease. Parasitol Today 1997;13:129-30.
  • 19. Urbina JA, Docampo R. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 2003;19:495-501.
  • 20. Urbina JA. Ergosterol biosynthesis and drug development for Chagas disease. Mem Inst Oswaldo Cruz RJ 2009;104:311-18.
  • 21. Urbina JA. Recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives. J Eukaryot Microbiol 2015;62:149-56.
  • 22. Cerisola JA. Serologic findings in patients with acute Chagas’ disease treated with Bay 2502. Bol Chil Parasitol 1969;24:54-9.
  • 23. Cerisola JA, Alvarez M, Lugones H, Rebosolan JB. Sensitivity of serological tests in the diagnosis of Chagas’ disease. Bol Chil Parasitol 1969;24:2-8.
  • 24. Schmunis GA, Szarfman A, Coarasa L, Guilleron C, Peralta JM. Anti-Trypanosoma cruzi agglutinins in acute human Chagas’ disease. Am J Trop Med Hyg 1980;29: 170-8.
  • 25. Cancado JR, Brener Z. Treatment of Chagas disease. In: Brener Z, Andrade Z, editors. Trypanosoma cruzi e Doenca de Chagas. Rio de Janeiro: Guanabara Koogan; 1979. p. 362-424.
  • 26. Viotti R, Vigliano C, Armenti H, Segura E. Treatment of chronic Chagas’ disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J 1994;127:151-62.
  • 27. Viotti R, Vigliano C, Alvarez MG, Lococo B, Petti M, Bertocchi G, et al. Impact of aetiological treatment on conventional and multiplex serology in chronic Chagas disease. PLoSNTD 2011;5:e1314.
  • 28. de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet 1996;348:1407-13.
  • 29. Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med 2006;144:724-34.
  • 30. Andrade SG, Freitas LA, Peyrol S, Pimentel AR, Sadigursky M. Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice. Bull World Health Org 1991;69: 191—7.
  • 31. Tarleton RL, Zhang L, Downs MO. “Autoimmune rejection” of neonatal heart transplants in experimental Chagas disease is a parasite-specific response to infected host tissue. Proc Natl Acad Sci USA 1997;94:3932-7.
  • 32. Tarleton RL, Zhang L. Chagas disease etiology: autoimmunity or parasite persistence? Parasitol Today 1999;15:94-9.
  • 33. Docampo R, Moreno SN. Biochemical toxicology of antiparasitic drugs used in the chemotherapy and chemoprophylaxis of American trypanosomiasis (Chagas’ disease). Rev Biochem Toxicol 1985;7:159-204.
  • 34. Docampo R, Moreno SN. Bisphosphonates as chemotherapeutic agents against trypa- nosomatid and apicomplexan parasites. Curr Drug Targets Infect Disord 2001;1: 51-61.
  • 35. Gelb MH, Van Voorhis WC, Buckner FS, Yokoyama K, Eastman R, Carpenter EP, et al. Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics. Mol Biochem Parasitol 2003;126:155-63.
  • 36. Eberl M, Hintz M, Reichenberg A, Kollas AK, Wiesner J, Jomaa H. Microbial isopren- oid biosynthesis and human gammadelta T cell activation. FEBS Lett 2003;544:4-10.
  • 37. Banthorpe DV, Charlwood BV, Francis MJ. The biosynthesis of monoterpenes. Sogo Kango 1972;72:115-55.
  • 38. Montalvetti A, Bailey BN, Martin MB, Severin GW, Oldfield E, Docampo R. Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. J Biol Chem 2001;276:33930-7.
  • 39. Ferella M, Montalvetti A, Rohloff P, Miranda K, Fang J, Reina S, et al. A solanesyl- diphosphate synthase localizes in glycosomes of Trypanosoma cruzi. J Biol Chem 2006;281:39339-48.
  • 40. Ferella M, Li ZH, Andersson B, Docampo R. Farnesyl diphosphate synthase localizes to the cytoplasm of Trypanosoma cruzi and T. brucei. Exp Parasitol 2008;119:308-12.
  • 41. Parsons M. Glycosomes: parasites and the divergence of peroxisomal purpose. Mol Microbiol 2004;53:717-24.
  • 42. Docampo R, Moreno SN, Turrens JF, Katzin AM, Gonzalez-Cappa SM, Stoppani AO. Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi. Mol Biochem Parasitol 1981;3:169-80.
  • 43. Parodi AJ, Quesada-Allue LA. Protein glycosylation in Trypanosoma cruzi. I. Characterization of dolichol-bound monosaccharides and oligosaccharides synthesized “in vivo.” JBiol Chem 1982;257:7637-40.
  • 44. Docampo R, de Boiso JF, Stoppani AO. Tricarboxylic acid cycle operation at the kinetoplast-mitochondrion complex of Trypanosoma cruzi. Biochim Biophys Acta 1978; 502:466-76.
  • 45. Cuevas IC, Rohloff P, Sanchez DO, Docampo R. Characterization of farnesylated protein tyrosine phosphatase TcPRL-1 from Trypanosoma cruzi. Eukaryot Cell 2005;4: 1550-61.
  • 46. Nepomuceno-Silva JL, Yokoyama K, de Mello LD, Mendonca SM, Paixao JC, Baron R, et al. TcRho1, a farnesylated Rho family homologue from Trypanosoma cruzi: cloning, trans-splicing, and prenylation studies. J Biol Chem 2001;276:29711-18.
  • 47. Yokoyama K, Trobridge P, Buckner FS, Scholten J, Stuart KD, Van Voorhis WC, et al. The effects of protein farnesyltransferase inhibitors on trypanosomatids: inhibition of protein farnesylation and cell growth. Mol Biochem Parasitol 1998;94:87-97.
  • 48. Niyogi S, Docampo R. A novel role of Rab11 in trafficking GPI-anchored trans-sialidase to the plasma membrane of Trypanosoma cruzi. Small GTPases 2015;6:8-10.
  • 49. Blanchard L, Karst F. Characterization of a lysine-to-glutamic acid mutation in a conservative sequence of farnesyl diphosphate synthase from Saccharomyces cerevisiae. Gene 1993;125:185-9.
  • 50. Song L, Poulter CD. Yeast farnesyl-diphosphate synthase: site-directed mutagenesis of residues in highly conserved prenyltransferase domains I and II. Proc Natl Acad Sci USA 1994;91(8):3044-8.
  • 51. Gabelli SB, McLellan JS, Montalvetti A, Oldfield E, Docampo R, Amzel LM. Structure and mechanism of the farnesyl diphosphate synthase from Trypanosoma cruzi: implications for drug design. Proteins 2006;62:80-8.
  • 52. Huang CH, Gabelli SB, Oldfield E, Amzel LM. Binding of nitrogen-containing bispho- sphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer. Proteins 2010;78:888-99.
  • 53. Aripirala S, Szajnman SH, Jakoncic J, Rodriguez JB, Docampo R, Gabelli SB, et al. Design, synthesis, calorimetry, and crystallographic analysis of 2-alkylaminoethyl-1,1-bisphospho- nates as inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase. J Med Chem 2012;55(14):6445-54.
  • 54. Rodan GA. Mechanisms of action of bisphosphonates. Annu Rev Pharmacol Toxicol 1998;38:375-88.
  • 55. Martin MB, Grimley JS, Lewis JC, Heath 3rd HT, Bailey BN, Kendrick H, et al. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy. J Med Chem 2001;44:909-16.
  • 56. Urbina JA, Moreno B, Vierkotter S, Oldfield E, Payares G, Sanoja C, et al. Trypanosoma cruzi contains major pyrophosphate stores, and its growth in vitro and in vivo is blocked by pyrophosphate analogs. J Biol Chem 1999;274:33609-15.
  • 57. Garzoni LR, Caldera A, Meirelles Mde N, de Castro SL, Docampo R, Meints GA, et al. Selective in vitro effects of the farnesyl pyrophosphate synthase inhibitor risedronate on Trypanosoma cruzi. Int J Antimicrob Agents 2004;23:273-85.
  • 58. Garzoni LR, Waghabi MC, Baptista MM, de Castro SL, Meirelles Mde N, Britto CC, et al. Antiparasitic activity of risedronate in a murine model of acute Chagas’ disease. Int J Antimicrob Agents 2004;23:286-90.
  • 59. Bouzahzah B, Jelicks LA, Morris SA, Weiss LM, Tanowitz HB. Risedronate in the treatment of Murine Chagas’ disease. Parasitol Res 2005;96:184-7.
  • 60. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171-99.
  • 61. Ohnuma S, Koyama T, Ogura K. Purification of solanesyl-diphosphate synthase from Micrococcus luteus. A new class of prenyltransferase. J Biol Chem 1991;266:23706-13.
  • 62. Kawamukai M. Biosynthesis, bioproduction and novel roles of ubiquinone. J Biosci Bioeng 2002;94:511-17.
  • 63. Ashby MN, Kutsunai SY, Ackerman S, Tzagoloff A, Edwards PA. COQ2 is a candidate for the structural gene encoding para-hydroxybenzoate:polyprenyltransferase. J Biol Chem 1992;267:4128-36.
  • 64. Forsgren M, Attersand A, Lake S, Grunler J, Swiezewska E, Dallner G, et al. Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ. Biochem J 2004;382:519-26.
  • 65. Szajnman SH, Garcia Linares GE, Li ZH, Jiang C, Galizzi M, Bontempi EJ, et al. Synthesis and biological evaluation of 2-alkylaminoethyl-1,1-bisphosphonic acids against Trypanosoma cruzi and Toxoplasma gondii targeting farnesyl diphosphate synthase. Bioorg Med Chem 2008;16:3283-90.
  • 66. Glomset JA, Gelb MH, Farnsworth CC. Prenyl proteins in eukaryotic cells: a new type of membrane anchor. Trends Biochem Sci 1990;15:139-42.
  • 67. Glomset JA, Farnsworth CC. Role of protein modification reactions in programming interactions between ras-related GTPases and cell membranes. Annu Rev Cell Biol 1994; 10:181-205.
  • 68. Yokoyama K, Goodwin GW, Ghomashchi F, Glomset J, Gelb MH. Protein prenyltrans- ferases. Biochem Soc Trans 1992;20:489-94.
  • 69. Casey PJ, Seabra MC. Protein prenyltransferases. J Biol Chem 1996;271:5289-92.
  • 70. Leonard DM. Ras farnesyltransferase: a new therapeutic target. J Med Chem 1997;40: 2971-90.
  • 71. Sealey-Cardona M, Cammerer S, Jones S, Ruiz-Perez LM, Brun R, Gilbert IH, et al. Kinetic characterization of squalene synthase from Trypanosoma cruzi: selective inhibition by quinuclidine derivatives. Antimicrob Agents Chemother 2007;51:2123-9.
  • 72. Veiga-Santos P, Li K, Lameira L, de Carvalho TM, Huang G, Galizzi M, et al. SQ109, a new drug lead for Chagas disease. Antimicrob Agents Chemother 2015;59:1950-61.
  • 73. Chao MN, Matiuzzi CE, Storey M, Li C, Szajnman SH, Docampo R, et al. Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii. ChemMedChem 2015;10:1094-108.
  • 74. Shang N, Li Q, Ko TP, Chan HC, Li J, Zheng Y, et al. Squalene synthase as a target for Chagas disease therapeutics. PLoS Pathog 2014;10:e1004114.
  • 75. Buckner FS, Griffin JH, Wilson AJ, Van Voorhis WC. Potent anti-Trypanosoma cruzi activities of oxidosqualene cyclase inhibitors. Antimicrob Agents Chemother 2001;45:1210-15.
  • 76. Benaim G, Sanders JM, Garcia-Marchan Y, Colina C, Lira R, Caldera AR, et al. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem 2006;49:892-9.
  • 77. Lepesheva GI, Zaitseva NG, Nes WD, Zhou W, Arase M, Liu J, et al. CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B’ helix defines substrate preferences of sterol 14alpha-demethylase. J Biol Chem 2006;281:3577-85.
  • 78. Chen CK, Leung SS, Guilbert C, Jacobson MP, McKerrow JH, Podust LM. Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. PLoS NTD 2010;4:e651.
  • 79. Lepesheva GI, Hargrove TY, Anderson S, Kleshchenko Y, Furtak V, Wawrzak Z, et al. Structural insights into inhibition of sterol 14alpha-demethylase in the human pathogen Trypanosoma cruzi. J Biol Chem 2010;285:25582-90.
  • 80. Hargrove TY, Wawrzak Z, Alexander PW, Chaplin JH, Keenan M, Charman SA, et al. Complexes of Trypanosoma cruzi sterol 14alpha-demethylase (CYP51) with two pyridine- based drug candidates for Chagas disease: structural basis for pathogen selectivity. J Biol Chem 2013;288:31602-15.
  • 81. McCabe RE, Remington JS, Araujo FG. Ketoconazole inhibition of intracellular multiplication of Trypanosoma cruzi and protection of mice against lethal infection with the organism. J Infect Dis 1984;150:594-601.
  • 82. Raether W, Seidenath H. Ketoconazole and other potent antimycotic azoles exhibit pronounced activity against Trypanosoma cruzi, Plasmodium berghei and Entamoeba histolytica in vivo. Z Parasitenkd 1984;70:135-8.
  • 83. Goad LJ, Berens RL, Marr JJ, Beach DH, Holz Jr. GG. The activity of ketoconazole and other azoles against Trypanosoma cruzi: biochemistry and chemotherapeutic action in vitro. Mol Biochem Parasitol 1989;32:179-89.
  • 84. Beach DH, Goad LJ, Holz Jr. GG. Effects of ketoconazole on sterol biosynthesis by Trypanosoma cruzi epimastigotes. Biochem Biophys Res Commun 1986;136:851-6.
  • 85. McCabe RE, Remington JS, Araujo FG. In vitro and in vivo effects of itraconazole against Trypanosoma cruzi. Am J Trop Med Hyg 1986;35:280-4.
  • 86. Urbina JA, Vivas J, Lazardi K, Molina J, Payares G, Piras MM, et al. Antiproliferative effects of delta 24(25) sterol methyl transferase inhibitors on Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Chemotherapy 1996;42:294-307.
  • 87. Docampo R, Moreno SN. Free radical metabolism of antiparasitic agents. Fed Proc 1986;45:2471-6.
  • 88. Boveris A, Sies H, Martino EE, Docampo R, Turrens JF, Stoppani AO. Deficient metabolic utilization of hydrogen peroxide in Trypanosoma cruzi. Biochem J 1980;188: 643-8.
  • 89. Docampo R, De Souza W, Cruz FS, Roitman I, Cover B, Gutteridge WE. Ultrastructural alterations and peroxide formation induced by naphthoquinones in different stages of Trypanosoma cruzi. Z Parasitenkd 1978;57:189-98.
  • 90. Docampo R, Cruz FS, Boveris A, Muniz RP, Esquivel DM. Lipid peroxidation and the generation of free radicals, superoxide anion, and hydrogen peroxide in beta- lapachone-treated Trypanosoma cruzi epimastigotes. Arch Biochem Biophys 1978;186: 292-7.
  • 91. Krauth-Siegel RL, Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta 2008;1780: 1236-48.
  • 92. Irigoin F, Cibils L, Comini MA, Wilkinson SR, Flohe L, Radi R. Insights into the redox biology of Trypanosoma cruzi: trypanothione metabolism and oxidant detoxification. Free Radic Biol Med 2008;45:733-42.
  • 93. Docampo R, de Boiso JF, Boveris A, Stoppani AO. Localization of peroxidase activity in Trypanosoma cruzi microbodies. Experientia 1976;32:972-5.
  • 94. Wilkinson SR, Obado SO, Mauricio IL, Kelly JM. Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum. Proc Natl Acad Sci USA 2002;99:13453-8.
  • 95. Boveris A, Stoppani AO. Hydrogen peroxide metabolism in Trypanosoma cruzi. Medicina (B Aires) 1978;38:259-65.
  • 96. Piacenza L, Zago MP, Peluffo G, Alvarez MN, Basombrio MA, Radi R. Enzymes of the antioxidant network as novel determiners of Trypanosoma cruzi virulence. Int J Parasitol 2009;39:1455-64.
  • 97. Taylor MC, Lewis MD, Fortes Francisco A, Wilkinson SR, Kelly JM. The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against oxidative stress but is not a determinant of virulence. PLoS NTD 2015;9:e0003707.
  • 98. Nogueira FB, Rodrigues JF, Correa MM, Ruiz JC, Romanha AJ, Murta SM. The level of ascorbate peroxidase is enhanced in benznidazole-resistant populations of Trypanosoma cruzi and its expression is modulated by stress generated by hydrogen peroxide. Mem Inst Oswaldo Cruz 2012;107:494-502.
  • 99. Wilkinson SR, Temperton NJ, Mondragon A, Kelly JM. Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi. J Biol Chem 2000;275:8220-5.
  • 100. Turrens JF. Possible role of the NADH-fumarate reductase in superoxide anion and hydrogen peroxide production in Trypanosoma brucei. Mol Biochem Parasitol 1987; 25:55-60.
  • 101. Docampo R, Lopes JN, Cruz FS, Souza W. Trypanosoma cruzi: ultrastructural and metabolic alterations of epimastigotes by beta-lapachone. Exp Parasitol 1977;42:142-9.
  • 102. Boveris A, Docampo R, Turrens JF, Stoppani AO. Effect of beta and alpha-lapachone on the production of H2O2 and on the growth of Trypanosoma cruzi. Rev Asoc Argent Microbiol 1977;9:54-61.
  • 103. Lopes JN, Cruz FS, Docampo R, Vasconcellos ME, Sampaio MC, Pinto AV, et al. In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi. Ann Trop Med Parasitol 1978;72:523-31.
  • 104. Boveris A, Docampo R, Turrens JF, Stoppani AO. Effect of beta-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi. Biochem J 1978;175:431-9.
  • 105. Cruz FS, Docampo R, Boveris A. Generation of superoxide anions and hydrogen peroxide from beta-lapachone in bacteria. Antimicrob Agents Chemother 1978;14:630-3.
  • 106. Cruz FS, Docampo R, de Souza W. Effect of beta-lapachone on hydrogen peroxide production in Trypanosoma cruzi. Acta Trop 1978;35:35-40.
  • 107. Boveris A, Stoppani AO, Docampo R, Cruz FS. Superoxide anion production and trypanocidal action of naphthoquinones on Trypanosoma cruzi. Comp Biochem Physiol C 1978;61C:327-9.
  • 108. Goncalves AM, Vasconcellos ME, Docampo R, Cruz FS, de Souza W, Leon W. Evaluation of the toxicity of 3-allyl-beta-lapachone against Trypanosoma cruzi bloodstream forms. Mol Biochem Parasitol 1980;1:167-76.
  • 109. Docampo R, Stoppani AO. Generation of superoxide anion and hydrogen peroxide induced by nifurtimox in Trypanosoma cruzi. Arch Biochem Biophys 1979;197: 317-21.
  • 110. Docampo R, Stoppani AO. Mechanism of the trypanocidal action of nifurtimox and other nitro-derivatives on Trypanosoma cruzi. Medicina (B Aires) 1980;40:10-16.
  • 111. Docampo R, Moreno SN, Stoppani AO, Leon W, Cruz FS, Villalta F, et al. Mechanism of nifurtimox toxicity in different forms of Trypanosoma cruzi. Biochem Pharmacol 1981;30:1947-51.
  • 112. Faundez M, Pino L, Letelier P, Ortiz C, Lopez R, Seguel C, et al. Buthionine sulfoxi- mine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi. Antimicrob Agents Chemother 2005;49:126-30.
  • 113. Algranati ID. Polyamine metabolism in Trypanosoma cruzi: studies on the expression and regulation of heterologous genes involved in polyamine biosynthesis. Amino Acids 2010;38:645-51.
  • 114. Le Quesne SA, Fairlamb AH. Regulation of a high-affinity diamine transport system in Trypanosoma cruzi epimastigotes. Biochem J 1996;316:481-6.
  • 115. Carrillo C, Canepa GE, Algranati ID, Pereira CA. Molecular and functional characterization of a spermidine transporter (TcPAT12) from Trypanosoma cruzi. Biochem Biophys Res Commun 2006;344:936-40.
  • 116. Oza SL, Tetaud E, Ariyanayagam MR, Warnon SS, Fairlamb AH. A single enzyme catalyses formation of trypanothione from glutathione and spermidine in Trypanosoma cruzi. J Biol Chem 2002;277(39):35853-61.
  • 117. Jockers-Scherubl MC, Schirmer RH, Krauth-Siegel RL. Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds. Eur J Biochem 1989;180:267-72.
  • 118. Oza SL, Ariyanayagam MR, Fairlamb AH. Characterization of recombinant glutathio- nylspermidine synthetase/amidase from Crithidia fasciculata. Biochem J 2002;364: 679 86.
  • 119. Torrie LS, Wyllie S, Spinks D, Oza SL, Thompson S, Harrison JR, et al. Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis. JBiol Chem 2009;284:36137-45.
  • 120. Ariyanayagam MR, Fairlamb AH. Ovothiol and trypanothione as antioxidants in trypa- nosomatids. Mol Biochem Parasitol 2001;115:189-98.
  • 121. Ariyanayagam MR, Oza SL, Mehlert A, Fairlamb AH. Bis(glutathionyl)spermine and other novel trypanothione analogues in Trypanosoma cruzi. J Biol Chem 2003;278:27612-19.
  • 122. Rohloff P, Rodrigues CO, Docampo R. Regulatory volume decrease in Trypanosoma cruzi involves amino acid efflux and changes in intracellular calcium. Mol Biochem Parasitol 2003;126:219-30.
  • 123. Krauth-Siegel RL, Enders B, Henderson GB, Fairlamb AH, Schirmer RH. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur J Biochem 1987;164:123-8.
  • 124. Borges A, Cunningham ML, Tovar J, Fairlamb AH. Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase. Eur J Biochem 1995;228:745-52.
  • 125. Zhang Y, Bond CS, Bailey S, Cunningham ML, Fairlamb AH, Hunter WN. The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2. 3 A resolution. Protein Sci 1996;5:52-61.
  • 126. Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WN. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 1999;7:81-9.
  • 127. Krauth-Siegel RL, Sticherling C, Jost I, Walsh CT, Pai EF, Kabsch W, et al. Crystallization and preliminary crystallographic analysis of trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas’ disease. FEBS Lett 1993;317: 105-8.
  • 128. Lantwin CB, Schlichting I, Kabsch W, Pai EF, Krauth-Siegel RL. The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state. Proteins 1994;18:161-73.
  • 129. Jacoby EM, Schlichting I, Lantwin CB, Kabsch W, Krauth-Siegel RL. Crystal structure of the Trypanosoma cruzi trypanothione reductase.mepacrine complex. Proteins 1996; 24:73-80.
  • 130. Saravanamuthu A, Vickers TJ, Bond CS, Peterson MR, Hunter WN, Fairlamb AH. Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase: a template for drug design. J Biol Chem 2004;279:29493-500.
  • 131. Aguirre G, Cabrera E, Cerecetto H, Di Maio R, Gonzalez M, Seoane G, et al. Design, synthesis and biological evaluation of new potent 5-nitrofuryl derivatives as antiTrypanosoma cruzi agents. Studies of trypanothione binding site of trypanothione reductase as target for rational design. Eur J Med Chem 2004;39:421-31.
  • 132. Benson TJ, McKie JH, Garforth J, Borges A, Fairlamb AH, Douglas KT. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochem J 1992;286:9-11.
  • 133. Chan C, Yin H, Garforth J, McKie JH, Jaouhari R, Speers P, et al. Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J Med Chem 1998;41:148-56.
  • 134. Khan MO, Austin SE, Chan C, Yin H, Marks D, Vaghjiani SN, et al. Use of an additional hydrophobic binding site, the Z site, in the rational drug design of a new class of stronger trypanothione reductase inhibitor, quaternary alkylammonium phenothiazines. J Med Chem 2000;43:3148-56.
  • 135. Gutierrez-Correa J, Fairlamb AH, Stoppani AO. Trypanosoma cruzi trypanothione reductase is inactivated by peroxidase-generated phenothiazine cationic radicals. Free Radic Res 2001;34:363-78.
  • 136. Moreno SN, Carnieri EG, Docampo R. Inhibition of Trypanosoma cruzi trypanothione reductase by crystal violet. Mol Biochem Parasitol 1994;67:313-20.
  • 137. Baillet S, Buisine E, Horvath D, Maes L, Bonnet B, Sergheraert C. 2-Amino diphenyl- sulfides as inhibitors of trypanothione reductase: modification of the side chain. Bioorg MedChem 1996;4:891-9.
  • 138. O’Sullivan MC, Dalrymple DM, Zhou Q. Inhibiting effects of spermidine derivatives on Trypanosoma cruzi trypanothione reductase. J Enzyme Inhib 1996;11:97-114.
  • 139. Bonnet B, Soullez D, Davioud-Charvet E, Landry V, Horvath D, Sergheraert C. New spermine and spermidine derivatives as potent inhibitors of Trypanosoma cruzi trypa- nothione reductase. Bioorg Med Chem 1997;5:1249-56.
  • 140. O’Sullivan MC, Zhou Q, Li Z, Durham TB, Rattendi D, Lane S, et al. Polyamine derivatives as inhibitors of trypanothione reductase and assessment of their trypanocidal activities. Bioorg Med Chem 1997;5:2145-55.
  • 141. Li Z, Fennie MW, Ganem B, Hancock MT, Kobaslija M, Rattendi D, et al. Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents. Bioorg Med Chem Lett 2001;11:251-4.
  • 142. Garforth J, Yin H, McKie JH, Douglas KT, Fairlamb AH. Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenzazepines based on imipramine. J Enzyme Inhib 1997;12:161-73.
  • 143. Fournet A, Inchausti A, Yaluff G, Rojas De Arias A, Guinaudeau H, Bruneton J, et al. Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase. J Enzyme Inhib 1998;13:1-9.
  • 144. Gallwitz H, Bonse S, Martinez-Cruz A, Schlichting I, Schumacher K, Krauth-Siegel RL. Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies. J Med Chem 1999;42:364-72.
  • 145. Bonse S, Santelli-Rouvier C, Barbe J, Krauth-Siegel RL. Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships. J Med Chem 1999;42:5448-54.
  • 146. Bonse S, Richards JM, Ross SA, Lowe G, Krauth-Siegel RL. (2,2’:6’,2’’-Terpyridine) platinum(II) complexes are irreversible inhibitors of Trypanosoma cruzi trypanothione reductase but not of human glutathione reductase. J Med Chem 2000;43:4812-21.
  • 147. Lee B, Bauer H, Melchers J, Ruppert T, Rattray L, Yardley V, et al. Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem 2005;48:7400-10.
  • 148. Cota BB, Rosa LH, Fagundes EM, Martins-Filho OA, Correa-Oliveira R, Romanha AJ, et al. A potent trypanocidal component from the fungus Lentinus strigosus inhibits trypanothione reductase and modulates PBMC proliferation. Mem Inst Oswaldo Cruz 2008;103:263-70.
  • 149. Holloway GA, Baell JB, Fairlamb AH, Novello PM, Parisot JP, Richardson J, et al. Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening. Bioorg Med Chem Lett 2007;17:1422-7.
  • 150. Holloway GA, Charman WN, Fairlamb AH, Brun R, Kaiser M, Kostewicz E, et al. Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with antiparasitic activity. Antimicrob Agents Chemother 2009;53:2824-33.
  • 151. Logan FJ, Taylor MC, Wilkinson SR, Kaur H, Kelly JM. The terminal step in vitamin C biosynthesis in Trypanosoma cruzi is mediated by a FMN-dependent galactonolac- tone oxidase. Biochem J 2007;407:419-26.
  • 152. Wilkinson SR, Meyer DJ, Taylor MC, Bromley EV, Miles MA, Kelly JM. The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin. J Biol Chem 2002;277: 17062-71.
  • 153. Wilkinson SR, Meyer DJ, Kelly JM. Biochemical characterization of a trypanosome enzyme with glutathione-dependent peroxidase activity. Biochem J 2000;352:755-61.
  • 154. Patel S, Hussain S, Harris R, Sardiwal S, Kelly JM, Wilkinson SR, et al. Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I). Biochem J 2010;425:513-22.
  • 155. Wilkinson SR, Taylor MC, Touitha S, Mauricio IL, Meyer DJ, Kelly JM. TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum. Biochem J 2002;364:787-94.
  • 156. Guerrero SA, Lopez JA, Steinert P, Montemartini M, Kalisz HM, Colli W, et al. His-tagged tryparedoxin peroxidase of Trypanosoma cruzi as a tool for drug screening. Appl Microbiol Biotechnol 2000;53:410-14.
  • 157. Lopez JA, Carvalho TU, de Souza W, Flohe L, Guerrero SA, Montemartini M, et al. Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi. Free Radic Biol Med 2000;28:767-72.
  • 158. Thomson L, Denicola A, Radi R. The trypanothione-thiol system in Trypanosoma cruzi as a key antioxidant mechanism against peroxynitrite-mediated cytotoxicity. Arch Biochem Biophys 2003;412:55-64.
  • 159. Trujillo M, Budde H, Pineyro MD, Stehr M, Robello C, Flohe L, et al. Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically detoxify peroxy- nitrite via oxidation of fast reacting thiols. J Biol Chem 2004;279:34175-82.
  • 160. Piacenza L, Peluffo G, Alvarez MN, Kelly JM, Wilkinson SR, Radi R. Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously-derived peroxynitrite. Biochem J 2008;410:59-68.
  • 161. Pineyro MD, Arcari T, Robello C, Radi R, Trujillo M. Tryparedoxin peroxidases from Trypanosoma cruzi: high efficiency in the catalytic elimination of hydrogen peroxide and peroxynitrite. Arch Biochem Biophys 2011;507:287-95.
  • 162. Nogueira FB, Ruiz JC, Robello C, Romanha AJ, Murta SM. Molecular characterization of cytosolic and mitochondrial tryparedoxin peroxidase in Trypanosoma cruzi populations susceptible and resistant to benznidazole. Parasitol Res 2009;104: 835-44.
  • 163. Pineyro MD, Pizarro JC, Lema F, Pritsch O, Cayota A, Bentley GA, et al. Crystal structure of the tryparedoxin peroxidase from the human parasite Trypanosoma cruzi. J Struct Biol 2005;150:11-22.
  • 164. Alvarez MN, Peluffo G, Piacenza L, Radi R. Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: consequences for oxidative killing and role of microbial peroxiredoxins in infectivity. J Biol Chem 2011;286:6627-40.
  • 165. Ismail SO, Paramchuk W, Skeiky YA, Reed SG, Bhatia A, Gedamu L. Molecular cloning and characterization of two iron superoxide dismutase cDNAs from Trypanosoma cruzi. Mol Biochem Parasitol 1997;86:187-97.
  • 166. Temperton NJ, Wilkinson SR, Meyer DJ, Kelly JM. Overexpression of superoxide dismutase in Trypanosoma cruzi results in increased sensitivity to the trypanocidal agents gentian violet and benznidazole. Mol Biochem Parasitol 1998;96:167-76.
  • 167. Martinez A, Peluffo G, Petruk AA, Hugo M, Pineyro D, Demicheli V, et al. Structural and molecular basis of the peroxynitrite-mediated nitration and inactivation of Trypanosoma cruzi iron-superoxide dismutases (Fe-SODs) A and B: disparate susceptibilities due to the repair of Tyr35 radical by Cys83 in Fe-SODB through intramolecular electron transfer. J Biol Chem 2014;289:12760-78.
  • 168. Meshnick SR, Kitchener KR, Trang NL. Trypanosomatid iron-superoxide dismutase inhibitors. Selectivity and mechanism of N1, N6-bis(2,3-dihydroxybenzoyl)-1,6-diami- nohexane. Biochem Pharmacol 1985;34:3147-52.
  • 169. Olmo F, Urbanova K, Rosales MJ, Martin-Escolano R, Sanchez-Moreno M, Marin C. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase. Int J Parasitol Drugs Drug Resist 2015;5:110-16.
  • 170. Kubata BK, Kabututu Z, Nozaki T, Munday CJ, Fukuzumi S, Ohkubo K, et al. A key role for old yellow enzyme in the metabolism of drugs by Trypanosoma cruzi. J Exp Med 2002;196:1241-51.
  • 171. Wilkinson SR, Taylor MC, Horn D, Kelly JM, Cheeseman I. A mechanism for crossresistance to nifurtimox and benznidazole in trypanosomes. Proc Natl Acad Sci USA 2008;105:5022-7.
  • 172. Hall BS, Bot C, Wilkinson SR. Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J Biol Chem 2011;286:13088-95.
  • 173. Mason RP, Holtzman JL. The mechanism of microsomal and mitochondrial nitroreductase. Electron spin resonance evidence for nitroaromatic free radical intermediates. Biochemistry 1975;14:1626-32.
  • 174. Boiani M, Piacenza L, Hernandez P, Boiani L, Cerecetto H, Gonzalez M, et al. Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi: is oxidative stress involved? Biochem Pharmacol 2010;79:1736-45.
  • 175. Giulivi C, Turrens JF, Boveris A. Chemiluminescence enhancement by trypanocidal drugs and by inhibitors of antioxidant enzymes in Trypanosoma cruzi. Mol Biochem Parasitol 1988;30:243-51.
  • 176. Maya JD, Repetto Y, Agosin M, Ojeda JM, Tellez R, Gaule C, et al. Effects of nifurti- mox and benznidazole upon glutathione and trypanothione content in epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi. Mol Biochem Parasitol 1997;86:101-6.
  • 177. Moreno SN, Docampo R, Mason RP, Leon W, Stoppani AO. Different behaviors of benznidazole as free radical generator with mammalian and Trypanosoma cruzi microsomal preparations. Arch Biochem Biophys 1982;218:585-91.
  • 178. Hall BS, Wilkinson SR. Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrob Agents Chemother 2012;56:115-23.
  • 179. Trochine A, Creek DJ, Faral-Tello P, Barrett MP, Robello C. Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics. PLoS NTD 2014;8:e2844.
  • 180. Docampo R, Moreno SN, Muniz RP, Cruz FS, Mason RP. Light-enhanced free radical formation and trypanocidal action of gentian violet (crystal violet). Science 1983;220: 1292-5.
  • 181. Reszka K, Cruz FS, Docampo R. Photosensitization by the trypanocidal agent crystal violet. Type I versus type II reactions. Chem Biol Interact 1986;58:161-72.
  • 182. Docampo R, Moreno SN, Cruz FS. Enhancement of the cytotoxicity of crystal violet against Trypanosoma cruzi in the blood by ascorbate. Mol Biochem Parasitol 1988;27:241-7.
  • 183. Docampo R, de Souza W, Miranda K, Rohloff P, Moreno SN. Acidocalcisomes- conserved from bacteria to man. Nat Rev Microbiol 2005;3:251-61.
  • 184. Docampo R, Moreno SN. The acidocalcisome as a target for chemotherapeutic agents in protozoan parasites. Curr Pharm Des 2008;14:882-8.
  • 185. Moreno SN, Docampo R. The role of acidocalcisomes in parasitic protists. J Eukaryot Microbiol 2009;56:208-13.
  • 186. Docampo R, Moreno SN. Acidocalcisomes. Cell Calcium 2011;50:113-19.
  • 187. Kollien AH, Grospietsch T, Kleffmann T, Zerbst-Boroffka I, Schaub GA. Ionic composition of the rectal contents and excreta of the reduviid bug Triatoma infestans. J Insect Physiol 2001;47:739-47.
  • 188. Kollien AH, Schaub GA. The development of Trypanosoma cruzi in triatominae. Parasitol Today 2000;16:381-7.
  • 189. Montalvetti A, Rohloff P, Docampo R. A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi. J Biol Chem 2004;279:38673-82.
  • 190. Rohloff P, Montalvetti A, Docampo R. Acidocalcisomes and the contractile vacuole complex are involved in osmoregulation in Trypanosoma cruzi. J Biol Chem 2004;279:52270-81.
  • 191. Rohloff P, Docampo R. A contractile vacuole complex is involved in osmoregulation in Trypanosoma cruzi. Exp Parasitol 2008;118:17-24.
  • 192. Li ZH, Alvarez VE, De Gaudenzi JG, Sant’Anna C, Frasch AC, Cazzulo JJ, et al. Hyperosmotic stress induces aquaporin-dependent cell shrinkage, polyphosphate synthesis, amino acid accumulation, and global gene expression changes in Trypanosoma cruzi. J Biol Chem 2011;286:43959-71.
  • 193. Docampo R, Jimenez V, Lander N, Li ZH, Niyogi S. New insights into roles of acido- calcisomes and contractile vacuole complex in osmoregulation in protists. Int Rev Cell Mol Biol 2013;305:69-113.
  • 194. Niyogi S, Mucci J, Campetella O, Docampo R. Rab11 regulates trafficking of trans-sialidase to the plasma membrane through the contractile vacuole complex of Trypanosoma cruzi. PLoS Pathog 2014;10:e1004224.
  • 195. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, et al. Functional significance of cell volume regulatory mechanisms. Physiol Rev 1998;78:247-306.
  • 196. Lang F, Busch GL, Volkl H. The diversity of volume regulatory mechanisms. Cell Physiol Biochem 1998;8:1-45.
  • 197. Rohloff P, Docampo R. Ammonium production during hypo-osmotic stress leads to alkalinization of acidocalcisomes and cytosolic acidification in Trypanosoma cruzi. Mol Biochem Parasitol 2006;150:249-55.
  • 198. Schoijet AC, Miranda K, Medeiros LC, de Souza W, Flawia MM, Torres HN, et al. Defining the role of a FYVE domain in the localization and activity of a cAMP phosphodiesterase implicated in osmoregulation in Trypanosoma cruzi. Mol Microbiol 2011;79:50-62.
  • 199. King-Keller S, Li M, Smith A, Zheng S, Kaur G, Yang X, et al. Chemical validation of phosphodiesterase C as a chemotherapeutic target in Trypanosoma cru- zi, the etiological agent of Chagas’ disease. Antimicrob Agents Chemother 2010;54: 3738-45.
  • 200. Scott DA, de Souza W, Benchimol M, Zhong L, Lu HG, Moreno SN, et al. Presence of a plant-like proton-pumping pyrophosphatase in acidocalcisomes of Trypanosoma cruzi. JBiol Chem 1998;273:22151-8.
  • 201. Hill JE, Scott DA, Luo S, Docampo R. Cloning and functional expression of a gene encoding a vacuolar-type proton-translocating pyrophosphatase from Trypanosoma cruzi. Biochem J 2000;351:281-8.
  • 202. Martinez R, Wang Y, Benaim G, Benchimol M, de Souza W, Scott DA, et al. A proton pumping pyrophosphatase in the Golgi apparatus and plasma membrane vesicles of Trypanosoma cruzi. Mol Biochem Parasitol 2002;120:205-13.
  • 203. Kim EJ, Zhen RG, Rea PA. Heterologous expression of plant vacuolar pyrophosphatase in yeast demonstrates sufficiency of the substrate-binding subunit for proton transport. Proc Natl Acad Sci USA 1994;91:6128-32.
  • 204. Fang J, Rohloff P, Miranda K, Docampo R. Ablation of a small transmembrane protein of Trypanosoma brucei (TbVTC1) involved in the synthesis of polyphosphate alters acidocalcisome biogenesis and function, and leads to a cytokinesis defect. Biochem J 2007;407:161-70.
  • 205. Lander N, Ulrich PN, Docampo R. Trypanosoma brucei vacuolar transporter chaperone 4 (TbVtc4) is an acidocalcisome polyphosphate kinase required for in vivo infection. J Biol Chem 2013;288:34205-16.
  • 206. Hothorn M, Neumann H, Lenherr ED, Wehner M, Rybin V, Hassa PO, et al. Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase. Science 2009;324:513-16.
  • 207. Ulrich PN, Lander N, Kurup SP, Reiss L, Brewer J, Soares Medeiros LC, et al. The acidocalcisome vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi. J Eukaryot Microbiol 2014;61:155-65.
  • 208. Ormerod WE. The study of volutin granules in trypanosomes. Trans R Soc Trop Med Hyg 1961;55:313-32.
  • 209. Macadam RF, Williamson J. Drug effects on the fine structure of Trypanosoma rhode- siense: suramin, tryparsamide and mapharside. Ann Trop Med Parasitol 1974;68: 301-6.
  • 210. Ormerod WE, Shaw JJ. A study of granules and other changes in phase-contrast appearance produced by chemotherapeutic agents in trypanosomes. Br J Pharmacol Chemother 1963;21:259-72.
  • 211. Ormerod WE. A study of basophilic inclusion bodies produced by chemotherapeutic agents in trypanosomes. Br J Pharmacol Chemother 1951;6:334-41.
  • 212. Mathis AM, Holman JL, Sturk LM, Ismail MA, Boykin DW, Tidwell RR, et al. Accumulation and intracellular distribution of antitrypanosomal diamidine compounds DB75 and DB820 in African trypanosomes. Antimicrob Agents Chemother 2006;50: 2185-91.
  • 213. Mathis AM, Bridges AS, Ismail MA, Kumar A, Francesconi I, Anbazhagan M, et al. Diphenyl furans and aza analogs: effects of structural modification on in vitro activity, DNA binding, and accumulation and distribution in trypanosomes. Antimicrob Agents Chemother 2007;51:2801-10.
 
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