Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Amino Acid and Polyamine Membrane Transporters in Trypanosoma cruzi: Biological Function and Evaluation as Drug Targets

Author(s): Melisa Sayé, Chantal Reigada, Lucrecia Gauna, Edward A. Valera-Vera, Claudio A. Pereira* and Mariana R. Miranda

Volume 26, Issue 36, 2019

Page: [6636 - 6651] Pages: 16

DOI: 10.2174/0929867326666190620094710

Price: $65

Abstract

Amino acids and polyamines are involved in relevant processes for the parasite Trypanosoma cruzi, like protein synthesis, stress resistance, life cycle progression, infection establishment and redox balance, among others. In addition to the biosynthetic routes of amino acids, T. cruzi possesses transport systems that allow the active uptake from the extracellular medium; and in the case of polyamines, the uptake is the unique way to obtain these compounds. The TcAAAP protein family is absent in mammals and its members are responsible for amino acid and derivative uptake, thus the TcAAAP permeases are not only interesting and promising therapeutic targets but could also be used to direct the entry of toxic compounds into the parasite.

Although there is a treatment available for Chagas disease, its limited efficacy in the chronic stage of the disease, as well as the side effects reported, highlight the urgent need to develop new therapies. Discovery of new drugs is a slow and cost-consuming process, and even during clinical trials the drugs can fail. In this context, drug repositioning is an interesting and recommended strategy by the World Health Organization since costs and time are significantly reduced.

In this article, amino acids and polyamines transport and their potential as therapeutic targets will be revised, including examples of synthetic drugs and drug repurposing.

Keywords: Trypanosoma cruzi, amino acid transport, polyamine transport, therapeutic target, drug discovery, drug repositioning, new therapies, chagas disease.

[1]
Chagas, C. Nova Tripanozomiaze Humana: Estudos Sobre a Morfolojia E O Ciclo Evolutivo Do Schizotrypanum Cruzi N. Gen., N. Sp., Ajente Etiolojico de Nova Entidade Morbida Do Homem. Mem. Inst. Oswaldo Cruz, 1909, 159-218.
[http://dx.doi.org/10.1590/S0074-02761909000200008]
[2]
Rassi, A., Jr; Rassi, A.; Marin-Neto, J.A. Chagas disease. Lancet, 2010, 375(9723), 1388-1402.
[http://dx.doi.org/10.1016/S0140-6736(10)60061-X] [PMID: 20399979]
[3]
Barrett, M.P.; Burchmore, R.J.; Stich, A.; Lazzari, J.O.; Frasch, A.C.; Cazzulo, J.J.; Krishna, S. The trypanosomiases. Lancet, 2003, 362(9394), 1469-1480.
[http://dx.doi.org/10.1016/S0140-6736(03)14694-6] [PMID: 14602444]
[4]
Pérez-Molina, J.A.; Norman, F.; López-Vélez, R. Chagas disease in non-endemic countries: epidemiology, clinical presentation and treatment. Curr. Infect. Dis. Rep., 2012, 14(3), 263-274.
[http://dx.doi.org/10.1007/s11908-012-0259-3] [PMID: 22477037]
[5]
Murcia, L.; Carrilero, B.; Munoz-Davila, M.J.; Thomas, M.C.; López, M.C.; Segovia, M. Risk factors and primary prevention of congenital Chagas disease in a nonendemic country. Clin. Infect. Dis., 2013, 56(4), 496-502.
[http://dx.doi.org/10.1093/cid/cis910] [PMID: 23097582]
[6]
Araujo, P.F.; Almeida, A.B.; Pimentel, C.F.; Silva, A.R.; Sousa, A.; Valente, S.A.; Valente, V.C.; Britto, M.M.; Rosa, A.C.; Alves, R.M.; Hagström, L.; Teixeira, A.R.L. Sexual transmission of American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites. Mem. Inst. Oswaldo Cruz, 2017, 112(6), 437-446.
[http://dx.doi.org/10.1590/0074-02760160538] [PMID: 28591404]
[7]
Sánchez, L.V.; Ramírez, J.D. Congenital and oral transmission of American trypanosomiasis: an overview of physiopathogenic aspects. Parasitology, 2013, 140(2), 147-159.
[http://dx.doi.org/10.1017/S0031182012001394] [PMID: 23010131]
[8]
World Health Organization. Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly. Epidemiol. Rec., 2015, 90(6), 33-43.
[PMID: 25671846]
[9]
Urbina, J.A. Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Trop., 2010, 115(1-2), 55-68.
[http://dx.doi.org/10.1016/j.actatropica.2009.10.023] [PMID: 19900395]
[10]
Urbina, J.A. Recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives. J. Eukaryot. Microbiol., 2015, 62(1), 149-156.
[http://dx.doi.org/10.1111/jeu.12184] [PMID: 25284065]
[11]
Morillo, C.A.; Marin-Neto, J.A.; Avezum, A.; Sosa-Estani, S.; Rassi, A., Jr; Rosas, F.; Villena, E.; Quiroz, R.; Bonilla, R.; Britto, C.; Guhl, F.; Velazquez, E.; Bonilla, L.; Meeks, B.; Rao-Melacini, P.; Pogue, J.; Mattos, A.; Lazdins, J.; Rassi, A.; Connolly, S.J.; Yusuf, S. BENEFIT Investigators. Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy. N. Engl. J. Med., 2015, 373(14), 1295-1306.
[http://dx.doi.org/10.1056/NEJMoa1507574] [PMID: 26323937]
[12]
Urbina, J.A.; Payares, G.; Contreras, L.M.; Liendo, A.; Sanoja, C.; Molina, J.; Piras, M.; Piras, R.; Perez, N.; Wincker, P.; Loebenberg, D. Antiproliferative effects and mechanism of action of SCH 56592 against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Antimicrob. Agents Chemother., 1998, 42(7), 1771-1777.
[http://dx.doi.org/10.1128/AAC.42.7.1771] [PMID: 9661019]
[13]
Molina, I.; Salvador, F.; Sánchez-Montalvá, A. The use of posaconazole against Chagas disease. Curr. Opin. Infect. Dis., 2015, 28(5), 397-407.
[http://dx.doi.org/10.1097/QCO.0000000000000192] [PMID: 26203852]
[14]
Molina, I.; Gómez i Prat, J.; Salvador, F.; Treviño, B.; Sulleiro, E.; Serre, N.; Pou, D.; Roure, S.; Cabezos, J.; Valerio, L.; Blanco-Grau, A.; Sánchez-Montalvá, A.; Vidal, X.; Pahissa, A. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N. Engl. J. Med., 2014, 370(20), 1899-1908.
[http://dx.doi.org/10.1056/NEJMoa1313122] [PMID: 24827034]
[15]
Morillo, C.A.; Waskin, H.; Sosa-Estani, S.; Del Carmen Bangher, M.; Cuneo, C.; Milesi, R.; Mallagray, M.; Apt, W.; Beloscar, J.; Gascon, J.; Molina, I.; Echeverria, L.E.; Colombo, H.; Perez-Molina, J.A.; Wyss, F.; Meeks, B.; Bonilla, L.R.; Gao, P.; Wei, B.; McCarthy, M.; Yusuf, S. STOP-CHAGAS investigators. benznidazole and posaconazole in eliminating parasites in asymptomatic t. cruzi carriers: The STOP-CHAGAS trial. J. Am. Coll. Cardiol., 2017, 69(8), 939-947.
[http://dx.doi.org/10.1016/j.jacc.2016.12.023] [PMID: 28231946]
[16]
Silber, A.M.; Colli, W.; Ulrich, H.; Alves, M.J.M.; Pereira, C.A. Amino acid metabolic routes in Trypanosoma cruzi: possible therapeutic targets against Chagas’ disease. Curr. Drug Targets Infect. Disord., 2005, 5(1), 53-64.
[http://dx.doi.org/10.2174/1568005053174636] [PMID: 15777198]
[17]
Ellington, W.R. Evolution and physiological roles of phosphagen systems. Annu. Rev. Physiol., 2001, 63, 289-325.
[http://dx.doi.org/10.1146/annurev.physiol.63.1.289] [PMID: 11181958]
[18]
Cunha-e-Silva, N.; Sant’Anna, C.; Pereira, M.G.; Porto-Carreiro, I.; Jeovanio, A.L.; de Souza, W. Reservosomes: multipurpose organelles? Parasitol. Res., 2006, 99(4), 325-327.
[http://dx.doi.org/10.1007/s00436-006-0190-3] [PMID: 16794853]
[19]
Marciano, D.; Llorente, C.; Maugeri, D.A.; de la Fuente, C.; Opperdoes, F.; Cazzulo, J.J.; Nowicki, C. Biochemical characterization of stage-specific isoforms of aspartate aminotransferases from Trypanosoma cruzi and Trypanosoma brucei. Mol. Biochem. Parasitol., 2008, 161(1), 12-20.
[http://dx.doi.org/10.1016/j.molbiopara.2008.05.005] [PMID: 18602174]
[20]
Cazzulo, J.J. Intermediate metabolism in Trypanosoma cruzi. J. Bioenerg. Biomembr., 1994, 26(2), 157-165.
[http://dx.doi.org/10.1007/BF00763064] [PMID: 8056782]
[21]
Paes, L.S.; Suárez Mantilla, B.; Zimbres, F.M.; Pral, E.M.F.; Diogo de Melo, P.; Tahara, E.B.; Kowaltowski, A.J.; Elias, M.C.; Silber, A.M. Proline dehydrogenase regulates redox state and respiratory metabolism in Trypanosoma cruzi. PLoS One, 2013, 8(7)e69419
[http://dx.doi.org/10.1371/journal.pone.0069419] [PMID: 23894476]
[22]
Mantilla, B.S.; Paes, L.S.; Pral, E.M.F.; Martil, D.E.; Thiemann, O.H.; Fernández-Silva, P.; Bastos, E.L.; Silber, A.M. Role of Δ1-pyrroline-5-carboxylate dehydrogenase supports mitochondrial metabolism and host-cell invasion of Trypanosoma cruzi. J. Biol. Chem., 2015, 290(12), 7767-7790.
[http://dx.doi.org/10.1074/jbc.M114.574525] [PMID: 25623067]
[23]
Crispim, M.; Damasceno, F.S.; Hernández, A.; Barisón, M.J.; Pretto Sauter, I.; Souza Pavani, R.; Santos Moura, A.; Pral, E.M.F.; Cortez, M.; Elias, M.C.; Silber, A.M. The glutamine synthetase of Trypanosoma cruzi is required for its resistance to ammonium accumulation and evasion of the parasitophorous vacuole during host-cell infection. PLoS Negl. Trop. Dis., 2018, 12(1)e0006170
[http://dx.doi.org/10.1371/journal.pntd.0006170] [PMID: 29320490]
[24]
Canepa, G.E.; Bouvier, L.A.; Urias, U.; Miranda, M.R.; Colli, W.; Alves, M.J.M.; Pereira, C.A. Aspartate transport and metabolism in the protozoan parasite Trypanosoma cruzi. FEMS Microbiol. Lett., 2005, 247(1), 65-71.
[http://dx.doi.org/10.1016/j.femsle.2005.04.029] [PMID: 15927749]
[25]
Wallace, H.M.; Fraser, A.V.; Hughes, A. A perspective of polyamine metabolism. Biochem. J., 2003, 376(Pt 1), 1-14.
[http://dx.doi.org/10.1042/bj20031327] [PMID: 13678416]
[26]
Fairlamb, A.; Blackburn, P.; Ulrich, P.; Chait, B.; Cerami, A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science, 1985, 227(4693), 1485-1487.
[http://dx.doi.org/10.1126/science.3883489] [PMID: 3883489]
[27]
Carrillo, C.; Cejas, S.; González, N.S.; Algranati, I.D. Trypanosoma cruzi epimastigotes lack ornithine decarboxylase but can express a foreign gene encoding this enzyme. FEBS Lett., 1999, 454(3), 192-196.
[http://dx.doi.org/10.1016/S0014-5793(99)00804-2] [PMID: 10431805]
[28]
Carrillo, C.; Cejas, S.; Huber, A.; González, N.S.; Algranati, I.D. Lack of arginine decarboxylase in Trypanosoma cruzi epimastigotes. J. Eukaryot. Microbiol., 2003, 50(5), 312-316.
[http://dx.doi.org/10.1111/j.1550-7408.2003.tb00141.x] [PMID: 14563168]
[29]
Busch, W.; Saier, M.H. Jr. The transporter classification (TC) system, 2002. Crit. Rev. Biochem. Mol. Biol., 2002, 37(5), 287-337.
[http://dx.doi.org/10.1080/10409230290771528] [PMID: 12449427]
[30]
Hampton, J.R. Lysine uptake in cultured Trypanosoma cruzi: interactions of competitive inhibitors. J. Protozool., 1970, 17(4), 597-600.
[http://dx.doi.org/10.1111/j.1550-7408.1970.tb04734.x] [PMID: 5505361]
[31]
Hampton, J.R. Arginine transport in the culture form of Trypanosoma cruzi. J. Protozool., 1971, 18(4), 701-703.
[http://dx.doi.org/10.1111/j.1550-7408.1971.tb03400.x] [PMID: 4943764]
[32]
Goldgerg, S.S.; Pereira, A.A.; Chiari, E.; Mares-Guia, M.; Gazzinelli, G. Comparative kinetics of arginine and lysine transport by epimastigotes and trypomastigotes from two strains of Trypanosoma cruzi. J. Protozool., 1976, 23(1), 179-186.
[http://dx.doi.org/10.1111/j.1550-7408.1976.tb05267.x] [PMID: 775066]
[33]
González, N.S.; Ceriani, C.; Algranati, I.D. Differential regulation of putrescine uptake in Trypanosoma cruzi and other trypanosomatids. Biochem. Biophys. Res. Commun., 1992, 188(1), 120-128.
[http://dx.doi.org/10.1016/0006-291X(92)92358-5] [PMID: 1417835]
[34]
Le Quesne, S.A.; Fairlamb, A.H. Regulation of a high-affinity diamine transport system in Trypanosoma cruzi epimastigotes. Biochem. J., 1996, 316(Pt 2), 481-486.
[http://dx.doi.org/10.1042/bj3160481] [PMID: 8687391]
[35]
Carrillo, C.; Canepa, G.E.; Algranati, I.D.; Pereira, C.A. Molecular and functional characterization of a spermidine transporter (TcPAT12) from Trypanosoma cruzi. Biochem. Biophys. Res. Commun., 2006, 344(3), 936-940.
[http://dx.doi.org/10.1016/j.bbrc.2006.03.215] [PMID: 16631600]
[36]
Pereira, C.A.; Alonso, G.D.; Paveto, M.C.; Flawiá, M.M.; Torres, H.N. L-arginine uptake and L-phosphoarginine synthesis in Trypanosoma cruzi. J. Eukaryot. Microbiol., 1999, 46(6), 566-570.
[http://dx.doi.org/10.1111/j.1550-7408.1999.tb05132.x] [PMID: 10568030]
[37]
White, M.F. The transport of cationic amino acids across the plasma membrane of mammalian cells. Biochim. Biophys. Acta, 1985, 822(3-4), 355-374.
[http://dx.doi.org/10.1016/0304-4157(85)90015-2] [PMID: 2933076]
[38]
Canepa, G.E.; Silber, A.M.; Bouvier, L.A.; Pereira, C.A. Biochemical characterization of a low-affinity arginine permease from the parasite Trypanosoma cruzi. FEMS Microbiol. Lett., 2004, 236(1), 79-84.
[http://dx.doi.org/10.1111/j.1574-6968.2004.tb09630.x] [PMID: 15212794]
[39]
Pereira, C.A.; Alonso, G.D.; Ivaldi, S.; Silber, A.; Alves, M.J.M.; Bouvier, L.A.; Flawiá, M.M.; Torres, H.N. Arginine metabolism in Trypanosoma cruzi is coupled to parasite stage and replication. FEBS Lett., 2002, 526(1-3), 111-114.
[http://dx.doi.org/10.1016/S0014-5793(02)03157-5] [PMID: 12208515]
[40]
Alonso, G.D.; Pereira, C.A.; Remedi, M.S.; Paveto, M.C.; Cochella, L.; Ivaldi, M.S.; Gerez de Burgos, N.M.; Torres, H.N.; Flawiá, M.M. Arginine kinase of the flagellate protozoa Trypanosoma cruzi. Regulation of its expression and catalytic activity. FEBS Lett., 2001, 498(1), 22-25.
[http://dx.doi.org/10.1016/S0014-5793(01)02473-5] [PMID: 11389891]
[41]
Silber, A.M.; Tonelli, R.R.; Martinelli, M.; Colli, W.; Alves, M.J.M. Active transport of L-proline in Trypanosoma cruzi. J. Eukaryot. Microbiol., 2002, 49(6), 441-446.
[http://dx.doi.org/10.1111/j.1550-7408.2002.tb00225.x] [PMID: 12503677]
[42]
Tonelli, R.R.; Silber, A.M.; Almeida-de-Faria, M.; Hirata, I.Y.; Colli, W.; Alves, M.J.M. L-proline is essential for the intracellular differentiation of Trypanosoma cruzi. Cell. Microbiol., 2004, 6(8), 733-741.
[http://dx.doi.org/10.1111/j.1462-5822.2004.00397.x] [PMID: 15236640]
[43]
Sayé, M.; Miranda, M.R.; Reigada, C.; Pereira, C.A. Trypanosoma cruzi proline transport presents a cell density-dependent regulation. J. Eukaryot. Microbiol., 2016, 63(4), 516-523.
[http://dx.doi.org/10.1111/jeu.12295] [PMID: 26750517]
[44]
Silber, A.M.; Rojas, R.L.G.; Urias, U.; Colli, W.; Alves, M.J.M. Biochemical characterization of the glutamate transport in Trypanosoma cruzi. Int. J. Parasitol., 2006, 36(2), 157-163.
[http://dx.doi.org/10.1016/j.ijpara.2005.10.006] [PMID: 16373069]
[45]
Nozaki, T.; Shigeta, Y.; Saito-Nakano, Y.; Imada, M.; Kruger, W.D. Characterization of transsulfuration and cysteine biosynthetic pathways in the protozoan hemoflagellate, Trypanosoma cruzi. Isolation and molecular characterization of cystathionine beta-synthase and serine acetyltransferase from Trypanosoma. J. Biol. Chem., 2001, 276(9), 6516-6523.
[http://dx.doi.org/10.1074/jbc.M009774200] [PMID: 11106665]
[46]
Canepa, G.E.; Bouvier, L.A.; Miranda, M.R.; Uttaro, A.D.; Pereira, C.A. Characterization of Trypanosoma cruzi L-cysteine transport mechanisms and their adaptive regulation. FEMS Microbiol. Lett., 2009, 292(1), 27-32.
[http://dx.doi.org/10.1111/j.1574-6968.2008.01467.x] [PMID: 19175408]
[47]
Inbar, E.; Canepa, G.E.; Carrillo, C.; Glaser, F.; Suter Grotemeyer, M.; Rentsch, D.; Zilberstein, D.; Pereira, C.A. Lysine transporters in human trypanosomatid pathogens. Amino Acids, 2012, 42(1), 347-360.
[http://dx.doi.org/10.1007/s00726-010-0812-z] [PMID: 21170560]
[48]
Manchola, N.C.; Rapado, L.N.; Barisón, M.J.; Silber, A.M. Biochemical characterization of branched chain amino acids uptake in Trypanosoma cruzi. J. Eukaryot. Microbiol., 2016, 63(3), 299-308.
[http://dx.doi.org/10.1111/jeu.12278] [PMID: 26496801]
[49]
Barisón, M.J.; Damasceno, F.S.; Mantilla, B.S.; Silber, A.M. The active transport of histidine and its role in ATP production in Trypanosoma cruzi. J. Bioenerg. Biomembr., 2016, 48(4), 437-449.
[http://dx.doi.org/10.1007/s10863-016-9665-9] [PMID: 27222029]
[50]
Harington, J.S. Studies of the amino acids of Rhodnius prolixus I. Analysis of the haemolymph. Parasitology, 1961, 51, 309-318.
[http://dx.doi.org/10.1017/S0031182000070554] [PMID: 13904705]
[51]
Harington, J.S. Studies of the amino acids of Rhodnius prolixus II. Analysis of the excretory material. Parasitology, 1961, 51, 319-326.
[http://dx.doi.org/10.1017/S0031182000070566] [PMID: 13904706]
[52]
Barrett, F.M.; Friend, W.G. Differences in the concentration of free amino acids in the haemolymph of adult male and female Rhodnius Prolixus. Comp. Biochem. Physiol. B, 1975, 52, 427-431.
[http://dx.doi.org/10.1016/0305-0491(75)90156-X] [PMID: 1183193]
[53]
Atwood, J.A., III; Weatherly, D.B.; Minning, T.A.; Bundy, B.; Cavola, C.; Opperdoes, F.R.; Orlando, R.; Tarleton, R.L. The Trypanosoma cruzi proteome. Science, 2005, 309(5733), 473-476.
[http://dx.doi.org/10.1126/science.1110289] [PMID: 16020736]
[54]
Saier, M.H. Jr.; Reddy, V.S.; Tsu, B.V.; Ahmed, M.S.; Li, C.; Moreno-Hagelsieb, G. The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res., 2016, 44(D1), D372-D379.
[http://dx.doi.org/10.1093/nar/gkv1103] [PMID: 26546518]
[55]
Jack, D.L.; Paulsen, I.T.; Saier, M.H. The amino acid/polyamine/organocation (APC) superfamily of transporters specific for amino acids, polyamines and organocations. Microbiology, 2000, 146(Pt 8), 1797-1814.
[http://dx.doi.org/10.1099/00221287-146-8-1797] [PMID: 10931886]
[56]
Young, G.B.; Jack, D.L.; Smith, D.W.; Saier, M.H. Jr. The amino acid/auxin:proton symport permease family. Biochim. Biophys. Acta, 1999, 1415(2), 306-322.
[http://dx.doi.org/10.1016/S0005-2736(98)00196-5] [PMID: 9889387]
[57]
Reizer, J.; Finley, K.; Kakuda, D.; MacLeod, C.L.; Reizer, A.; Saier, M.H. Jr. Mammalian integral membrane receptors are homologous to facilitators and antiporters of yeast, fungi, and eubacteria. Protein Sci., 1993, 2(1), 20-30.
[http://dx.doi.org/10.1002/pro.5560020103] [PMID: 8382989]
[58]
Reizer, J.; Reizer, A.; Saier, M.H. Jr A functional superfamily of sodium/solute symporters. Biochim. Biophys. Acta, 1994, 1197(2), 133-166.
[http://dx.doi.org/10.1016/0304-4157(94)90003-5] [PMID: 8031825]
[59]
Chang, H.C.; Bush, D.R. Topology of NAT2, a prototypical example of a new family of amino acid transporters. J. Biol. Chem., 1997, 272(48), 30552-30557.
[http://dx.doi.org/10.1074/jbc.272.48.30552] [PMID: 9374550]
[60]
Bouvier, L.A.; Silber, A.M.; Galvão Lopes, C.; Canepa, G.E.; Miranda, M.R.; Tonelli, R.R.; Colli, W.; Alves, M.J.; Pereira, C.A. Post genomic analysis of permeases from the amino acid/auxin family in protozoan parasites. Biochem. Biophys. Res. Commun., 2004, 321(3), 547-556.
[http://dx.doi.org/10.1016/j.bbrc.2004.07.002] [PMID: 15358142]
[61]
El-Sayed, N.M.; Myler, P.J.; Bartholomeu, D.C.; Nilsson, D.; Aggarwal, G.; Tran, A.N.; Ghedin, E.; Worthey, E.A.; Delcher, A.L.; Blandin, G.; Westenberger, S.J.; Caler, E.; Cerqueira, G.C.; Branche, C.; Haas, B.; Anupama, A.; Arner, E.; Aslund, L.; Attipoe, P.; Bontempi, E.; Bringaud, F.; Burton, P.; Cadag, E.; Campbell, D.A.; Carrington, M.; Crabtree, J.; Darban, H.; da Silveira, J.F.; de Jong, P.; Edwards, K.; Englund, P.T.; Fazelina, G.; Feldblyum, T.; Ferella, M.; Frasch, A.C.; Gull, K.; Horn, D.; Hou, L.; Huang, Y.; Kindlund, E.; Klingbeil, M.; Kluge, S.; Koo, H.; Lacerda, D.; Levin, M.J.; Lorenzi, H.; Louie, T.; Machado, C.R.; McCulloch, R.; McKenna, A.; Mizuno, Y.; Mottram, J.C.; Nelson, S.; Ochaya, S.; Osoegawa, K.; Pai, G.; Parsons, M.; Pentony, M.; Pettersson, U.; Pop, M.; Ramirez, J.L.; Rinta, J.; Robertson, L.; Salzberg, S.L.; Sanchez, D.O.; Seyler, A.; Sharma, R.; Shetty, J.; Simpson, A.J.; Sisk, E.; Tammi, M.T.; Tarleton, R.; Teixeira, S.; Van Aken, S.; Vogt, C.; Ward, P.N.; Wickstead, B.; Wortman, J.; White, O.; Fraser, C.M.; Stuart, K.D.; Andersson, B. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science, 2005, 309(5733), 409-415.
[http://dx.doi.org/10.10.1126/science.1112631] [PMID: 16020725]
[62]
Carrillo, C.; Canepa, G.E.; Giacometti, A.; Bouvier, L.A.; Miranda, M.R.; de los Milagros Camara, M.; Pereira, C.A. Trypanosoma cruzi amino acid transporter TcAAAP411 mediates arginine uptake in yeasts. FEMS Microbiol. Lett., 2010, 306(2), 97-102.
[http://dx.doi.org/10.1111/j.1574-6968.2010.01936.x] [PMID: 20337715]
[63]
Hasne, M.P.; Coppens, I.; Soysa, R.; Ullman, B. A high-affinity putrescine-cadaverine transporter from Trypanosoma cruzi. Mol. Microbiol., 2010, 76(1), 78-91.
[http://dx.doi.org/10.1111/j.1365-2958.2010.07081.x] [PMID: 20149109]
[64]
Soysa, R.; Venselaar, H.; Poston, J.; Ullman, B.; Hasne, M.P. Structural model of a putrescine-cadaverine permease from Trypanosoma cruzi predicts residues vital for transport and ligand binding. Biochem. J., 2013, 452(3), 423-432.
[http://dx.doi.org/10.1042/BJ20130350] [PMID: 23535070]
[65]
Reigada, C.; Sayé, M.; Vera, E.V.; Balcazar, D.; Fraccaroli, L.; Carrillo, C.; Miranda, M.R.; Pereira, C.A. Trypanosoma cruzi Polyamine transporter: its role on parasite growth and survival under stress conditions. J. Membr. Biol., 2016, 249(4), 475-481.
[http://dx.doi.org/10.1007/s00232-016-9888-z] [PMID: 26983938]
[66]
Miranda, M.R.; Sayé, M.; Bouvier, L.A. Cámara, Mde.L.; Montserrat, J.; Pereira, C.A. Cationic amino acid uptake constitutes a metabolic regulation mechanism and occurs in the flagellar pocket of Trypanosoma cruzi. PLoS One, 2012, 7(2)e32760
[http://dx.doi.org/10.1371/journal.pone.0032760] [PMID: 22393446]
[67]
Henriques, C.; Miller, M.P.; Catanho, M.; de Carvalho, T.M.U.; Krieger, M.A.; Probst, C.M.; de Souza, W.; Degrave, W.; Amara, S.G. Identification and functional characterization of a novel arginine/ornithine transporter, a member of a cationic amino acid transporter subfamily in the Trypanosoma cruzi genome. Parasit. Vectors, 2015, 8, 346.
[http://dx.doi.org/10.1186/s13071-015-0950-y] [PMID: 26109388]
[68]
Sayé, M.; Miranda, M.R.; di Girolamo, F.; de los Milagros Cámara, M.; Pereira, C.A. Proline modulates the Trypanosoma cruzi resistance to reactive oxygen species and drugs through a novel D, L-proline transporter. PLoS One, 2014, 9(3)e92028
[http://dx.doi.org/10.1371/journal.pone.0092028] [PMID: 24637744]
[69]
Inbar, E.; Schlisselberg, D.; Suter Grotemeyer, M.; Rentsch, D.; Zilberstein, D. A versatile proline/alanine transporter in the unicellular pathogen Leishmania donovani regulates amino acid homoeostasis and osmotic stress responses. Biochem. J., 2013, 449(2), 555-566.
[http://dx.doi.org/10.1042/BJ20121262] [PMID: 22994895]
[70]
Liburkin-Dan, T.; Schlisselberg, D.; Fischer-Weinberger, R.; Pescher, P.; Inbar, E.; Ephros, M.; Rentsch, D.; Späth, G.F.; Zilberstein, D. Stage-specific expression of the proline-alanine transporter in the human pathogen Leishmania. Mol. Biochem. Parasitol., 2018, 222, 1-5.
[http://dx.doi.org/10.1016/j.molbiopara.2018.04.002] [PMID: 29655799]
[71]
Barrett, M.P.; Gilbert, I.H. Targeting of toxic compounds to the trypanosome’s interior. Adv. Parasitol., 2006, 63, 125-183.
[http://dx.doi.org/10.1016/S0065-308X(06)63002-9] [PMID: 17134653]
[72]
Hofer, A.; Steverding, D.; Chabes, A.; Brun, R.; Thelander, L. Trypanosoma brucei CTP synthetase: a target for the treatment of African sleeping sickness. Proc. Natl. Acad. Sci. USA, 2001, 98(11), 6412-6416.
[http://dx.doi.org/10.1073/pnas.111139498] [PMID: 11353848]
[73]
Jaffe, J.J.; Voorheis, H.P.; McCormack, J.J., Jr Comparative effects of diverse mammalian sera on the uptake and protein incorporation of 14C-labelled amino acids by blood stream forms of T. brucei and T. rhodesiense in vitro. Trans. R. Soc. Trop. Med. Hyg., 1969, 63(1), 118-119.
[http://dx.doi.org/10.1016/0035-9203(69)90082-0] [PMID: 4978036]
[74]
Owolabi, O.A.; Wilson, C.; Molyneux, D.H.; Pentreath, V.W. Trypanocidal effects of catecholamines and indolealkylamines. Ann. Trop. Med. Parasitol., 1990, 84(2), 127-131.
[http://dx.doi.org/10.1080/00034983.1990.11812445] [PMID: 2383092]
[75]
Arrick, B.A.; Griffith, O.W.; Cerami, A. Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasis. J. Exp. Med., 1981, 153(3), 720-725.
[http://dx.doi.org/10.1084/jem.153.3.720] [PMID: 7252412]
[76]
Enanga, B.; Ariyanayagam, M.R.; Stewart, M.L.; Barrett, M.P. Activity of megazol, a trypanocidal nitroimidazole, is associated with DNA damage. Antimicrob. Agents Chemother., 2003, 47(10), 3368-3370.
[http://dx.doi.org/10.1128/AAC.47.10.3368-3370.2003] [PMID: 14506061]
[77]
Huynh, T.T.; Huynh, V.T.; Harmon, M.A.; Phillips, M.A. Gene knockdown of γ-glutamylcysteine synthetase by RNAi in the parasitic protozoa Trypanosoma brucei demonstrates that it is an essential enzyme. J. Biol. Chem., 2003, 278(41), 39794-39800.
[http://dx.doi.org/10.1074/jbc.M306306200] [PMID: 12888552]
[78]
Bacchi, C.J.; Nathan, H.C.; Hutner, S.H. McCann, P.P.; Sjoerdsma A. Polyamine metabolism - a potential therapeutic target in trypanosomes. Science, 210(4467), 332-334.
[http://dx.doi.org/10.1126/science.6775372] [PMID: 6775372]
[79]
Bacchi, C.J.; Yarlett, N. Effects of antagonists of polyamine metabolism on African trypanosomes. Acta Trop., 1993, 54(3-4), 225-236.
[http://dx.doi.org/10.1016/0001-706X(93)90095-S] [PMID: 7902660]
[80]
Vincent, I.M.; Creek, D.; Watson, D.G.; Kamleh, M.A.; Woods, D.J.; Wong, P.E.; Burchmore, R.J.S.; Barrett, M.P. A molecular mechanism for eflornithine resistance in African trypanosomes. PLoS Pathog., 2010, 6(11)e1001204
[http://dx.doi.org/10.1371/journal.ppat.1001204] [PMID: 21124824]
[81]
Carrillo, C.; González, N.S.; Algranati, I.D. Trypanosoma cruzi as a model system to study the expression of exogenous genes coding for polyamine biosynthetic enzymes. Induction of DFMO resistance in transgenic parasites. Biochim. Biophys. Acta, 2007, 1770(12), 1605-1611.
[http://dx.doi.org/10.1016/j.bbagen.2007.08.013] [PMID: 17920200]
[82]
Soares, C.O.; Alves, M.J.M.; Bechara, E.J.H. 1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation. Free Radic. Biol. Med., 2011, 50(12), 1760-1770.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.033] [PMID: 21466850]
[83]
Menezes, D.; Valentim, C.; Oliveira, M.F.; Vannier-Santos, M.A. Putrescine analogue cytotoxicity against Trypanosoma cruzi. Parasitol. Res., 2006, 98(2), 99-105.
[http://dx.doi.org/10.1007/s00436-005-0010-1] [PMID: 16283411]
[84]
Magdaleno, A.; Ahn, I.Y.; Paes, L.S.; Silber, A.M. Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C), on Trypanosoma cruzi. PLoS One, 2009, 4(2)e4534
[http://dx.doi.org/10.1371/journal.pone.0004534] [PMID: 19229347]
[85]
Sayé, M.; Fargnoli, L.; Reigada, C.; Labadie, G.R.; Pereira, C.A. Evaluation of proline analogs as trypanocidal agents through the inhibition of a Trypanosoma cruzi proline transporter. Biochim. Biophys. Acta, Gen. Subj., 2017, 1861(11 Pt A), 2913-2921.
[http://dx.doi.org/10.1016/j.bbagen.2017.08.015] [PMID: 28844978]
[86]
Algranati, I.D. Polyamine metabolism in Trypanosoma cruzi: studies on the expression and regulation of heterologous genes involved in polyamine biosynthesis. Amino Acids, 2010, 38(2), 645-651.
[http://dx.doi.org/10.1007/s00726-009-0425-6] [PMID: 19956988]
[87]
Reigada, C.; Phanstiel, O.I.V.; Miranda, M.R.; Pereira, C.A. Targeting polyamine transport in Trypanosoma cruzi. Eur. J. Med. Chem., 2018, 147, 1-6.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.083] [PMID: 29421567]
[88]
Reigada, C.; Valera-Vera, E.A.; Sayé, M.; Errasti, A.E.; Avila, C.C.; Miranda, M.R.; Pereira, C.A. Trypanocidal Effect of Isotretinoin through the Inhibition of Polyamine and Amino Acid Transporters in Trypanosoma cruzi. PLoS Negl. Trop. Dis., 2017, 11(3)e0005472
[http://dx.doi.org/10.1371/journal.pntd.0005472] [PMID: 28306713]
[89]
Alberca, L.N.; Sbaraglini, M.L.; Balcazar, D.; Fraccaroli, L.; Carrillo, C.; Medeiros, A.; Benitez, D.; Comini, M.; Talevi, A. Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning. J. Comput. Aided Mol. Des., 2016, 30(4), 305-321.
[http://dx.doi.org/10.1007/s10822-016-9903-6] [PMID: 26891837]
[90]
Dietrich, R.C.; Alberca, L.N.; Ruiz, M.D.; Palestro, P.H.; Carrillo, C.; Talevi, A.; Gavernet, L. Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening. Eur. J. Med. Chem., 2018, 149, 22-29.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.006] [PMID: 29494842]
[91]
Yorke, W. Recent Work on the Chemotherapy of Protozoal Infections. Trans. R. Soc. Trop. Med. Hyg., 1940, 33, 463-476.
[http://dx.doi.org/10.1016/S0035-9203(40)90029-3]
[92]
Wilkinson, S.R.; Kelly, J.M. Trypanocidal drugs: mechanisms, resistance and new targets. Expert Rev. Mol. Med., 2009, 11e31
[http://dx.doi.org/10.1017/S1462399409001252] [PMID: 19863838]
[93]
Díaz, M.V.; Miranda, M.R.; Campos-Estrada, C.; Reigada, C.; Maya, J.D.; Pereira, C.A.; López-Muñoz, R. Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi. Acta Trop., 2014, 134, 1-9.
[http://dx.doi.org/10.1016/j.actatropica.2014.02.012] [PMID: 24560964]
[94]
Balaña-Fouce, R.; Ordóñez, D.; Alunda, J.M. Putrescine transport system in Leishmania infantum promastigotes. Mol. Biochem. Parasitol., 1989, 35(1), 43-50.
[http://dx.doi.org/10.1016/0166-6851(89)90140-0] [PMID: 2503722]
[95]
Reguera, R.; Balaña Fouce, R.; Cubria, J.C.; Alvarez Bujidos, M.L.; Ordoñez, D. Putrescine uptake inhibition by aromatic diamidines in Leishmania infantum promastigotes. Biochem. Pharmacol., 1994, 47(10), 1859-1866.
[http://dx.doi.org/10.1016/0006-2952(94)90316-6] [PMID: 8204103]
[96]
Hasne, M.P.; Ullman, B. Identification and characterization of a polyamine permease from the protozoan parasite Leishmania major. J. Biol. Chem., 2005, 280(15), 15188-15194.
[http://dx.doi.org/10.1074/jbc.M411331200] [PMID: 15632173]
[97]
Seguel, V.; Castro, L.; Reigada, C.; Cortes, L.; Díaz, M.V.; Miranda, M.R.; Pereira, C.A.; Lapier, M.; Campos-Estrada, C.; Morello, A.; Kemmerling, U.; Maya, J.D.; López-Muñoz, R. Pentamidine antagonizes the benznidazole’s effect in vitro, and lacks of synergy in vivo: implications about the polyamine transport as an anti-Trypanosoma cruzi target. Exp. Parasitol., 2016, 171, 23-32.
[http://dx.doi.org/10.1016/j.exppara.2016.10.007] [PMID: 27729250]
[98]
Luna, K.P.; Hernández, I.P.; Rueda, C.M.; Zorro, M.M.; Croft, S.L.; Escobar, P. In vitro susceptibility of trypanosoma cruzi strains from Santander, Colombia, to hexadecylphosphocholine (miltefosine), nifurtimox and benznidazole. Biomedica, 2009, 29(3), 448-455.
[http://dx.doi.org/10.7705/biomedica.v29i3.15] [PMID: 20436996]
[99]
Kumar, S.; Stecher, G.; Tamura, K. MEGA7: molecular evolutionary genetics analysis version 7.0 for Bigger Datasets. Mol. Biol. Evol., 2016, 33(7), 1870-1874.
[http://dx.doi.org/10.1093/molbev/msw054] [PMID: 27004904]

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