ENTPDases from Pathogenic Trypanosomatids and Purinergic Signaling: Shedding Light towards Biotechnological Applications

Walmir       da Silva; Nancy       da Rocha Torres; Joice       de Melo Agripino; Victor    Hugo Ferraz    da Silva; Anna    Cláudia Alves    de Souza; Isadora    Cunha    Ribeiro; Tatiana    Aparecida    de Oliveira; Luciana    Angelo    de Souza; Lethicia    Kelly Ramos    Andrade; João    Victor Badaró   de Moraes; Marcel    Arruda    Diogo; Raíssa    Barbosa    de Castro; Marcelo    Depolo    Polêto; Luis    Carlos Crocco    Afonso; Juliana    Lopes Rangel    Fietto
doi:10.2174/1568026620666201005125146
Abstract

ENTPDases are enzymes known for hydrolyzing extracellular nucleotides and playing an essential role in controlling the nucleotide signaling via nucleotide/purinergic receptors P2. Moreover, ENTPDases, together with Ecto-5´-nucleotidase activity, affect the adenosine signaling via P1 receptors. These signals control many biological processes, including the immune system. In this context, ATP is considered as a trigger to inflammatory signaling, while adenosine (Ado) induces anti-inflammatory response. The trypanosomatids Leishmania and Trypanosoma cruzi, pathogenic agents of Leishmaniasis and Chagas Disease, respectively, have their own ENTPDases named “TpENTPDases,” which can affect the nucleotide signaling, adhesion and infection, in order to favor the parasite. Besides, TpENTPDases are essential for the parasite nutrition, since the Purine De Novo synthesis pathway is absent in them, which makes these pathogens dependent on the intake of purines and nucleopurines for the Salvage Pathway, in which TpENTPDases also take place. Here, we review information regarding TpNTPDases, including their known biological roles and their effect on the purinergic signaling. We also highlight the roles of these enzymes in parasite infection and their biotechnological applications, while pointing to future developments.
Keywords: ENTPDases, Purinergic signaling, Leishmaniasis, Chagas Disease, Parasites, Biotechnology.
« Previous Next »
Graphical Abstract

[1] 
Burnstock, G. Purine and pyrimidine receptors. Cell. Mol. Life Sci.,  2007, 64(12), 1471-1483.
[http://dx.doi.org/10.1007/s00018-007-6497-0] [PMID: 17375261] 
[2] 
Robson, S.C.; Sévigny, J.; Zimmermann, H. The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance. Purinergic Signal.,  2006, 2(2), 409-430.
[http://dx.doi.org/10.1007/s11302-006-9003-5] [PMID: 18404480] 
[3] 
Vasconcellos, Rde .S.; Mariotini-Moura, C.; Gomes, R.S.; Serafim,
    T.D.; Firmino, R. de C.; Silva E Bastos, M.; Castro, F.F.; Oliveira,
    C.M.; Borges-Pereira, L.; de Souza, A.C.A.; de Souza, R.F.;
    Gómez, G.A.T.; Pinheiro, A. da C.; Maciel, T.E.F.; Silva-Júnior,
    A.; Bressan, G.C.; Almeida, M.R.; Baqui, M.M.A.; Afonso, L.C.C.;
    Fietto, J.L.R. Leishmania infantum ecto-nucleoside triphosphate
    diphosphohydrolase-2 is an apyrase involved in macrophage
    infection and expressed in infected dogs. PLoS Negl. Trop. Dis.,  2014, 8(11)e3309
[http://dx.doi.org/10.1371/journal.pntd.0003309] [PMID: 25393008] 
[4] 
Fietto, J.L.R.; DeMarco, R.; Nascimento, I.P.; Castro, I.M.; Carvalho, T.M.U.; de Souza, W.; Bahia, M.T.; Alves, M.J.M.; Verjovski-Almeida, S. Characterization and immunolocalization of an NTP diphosphohydrolase of Trypanosoma cruzi. Biochem. Biophys. Res. Commun.,  2004, 316(2), 454-460.
[http://dx.doi.org/10.1016/j.bbrc.2004.02.071] [PMID: 15020239] 
[5] 
Sansom, F.M.; Robson, S.C.; Hartland, E.L. Possible effects of microbial ecto-nucleoside triphosphate diphosphohydrolases on host-pathogen interactions. Microbiol. Mol. Biol. Rev.,  2008, 72(4), 765-781.
[http://dx.doi.org/10.1128/MMBR.00013-08] [PMID: 19052327] 
[6] 
Souza, V. C.; Schlemmer, K.B.; Noal, C.B.; Jaques, J.A.; Zimmermann, C.E.; Leal, C.A.; Fleck, J.; Casali, E.A.; Morsch, V.M.; Schetinger, M.R.; Leal, D.B. E-NTPDase and E-ADA activities are altered in lymphocytes of patients with indeterminate form of Chagas’ disease. Parasitol. Int.,  2012, 61(4), 690-696.
[http://dx.doi.org/10.1016/j.parint.2012.07.008] [PMID: 22846899] 
[7] 
Cohn, C.S.; Gottlieb, M. The acquisition of purines by trypanosomatids.Parasitol. Today (Regul. Ed.); , 1997, 13, pp. (6)231-235.
[http://dx.doi.org/10.1016/S0169-4758(97)01059-4] [PMID: 15275076] 
[8] 
Paletta-Silva, R.; Meyer-Fernandes, J.R. Adenosine and immune imbalance in visceral leishmaniasis: the possible role of ectonucleotidases. J. Trop. Med.,  2012, 2012650874
[http://dx.doi.org/10.1155/2012/650874] [PMID: 22007242] 
[9] 
de Figueiredo, A.B.; Souza-Testasicca, M.C.; Afonso, L.C.C. Purinergic signaling and infection by Leishmania: A new approach to evasion of the immune response. Biomed. J.,  2016, 37(4), 244-250.
[10] 
Paes-Vieira, L.; Gomes-Vieira, A.L.; Meyer-Fernandes, J.R. NTPDase activities: possible roles on Leishmania spp infectivity and virulence. Cell Biol. Int.,  2018, 42(6), 670-682.
[http://dx.doi.org/10.1002/cbin.10944] [PMID: 29384228] 
[11] 
Sansom, F.M.; Ralton, J.E.; Sernee, M.F.; Cohen, A.M.; Hooker, D.J.; Hartland, E.L.; Naderer, T.; McConville, M.J. Golgi-located NTPDase1 of Leishmania major is required for lipophosphoglycan elongation and normal lesion development whereas secreted NTPDase2 is dispensable for virulence. PLoS Negl. Trop. Dis.,  2014, 8(12)e3402
[http://dx.doi.org/10.1371/journal.pntd.0003402] [PMID: 25521752] 
[12] 
Gomes, R.S.; de Carvalho, L.C.F.; de Souza Vasconcellos, R.; Fietto, J.L.R.; Afonso, L.C.C. E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase) of Leishmania amazonensis inhibits macrophage activation. Microbes Infect.,  2015, 17(4), 295-303.
[http://dx.doi.org/10.1016/j.micinf.2014.12.009] [PMID: 25554487] 
[13] 
Mantuano-Barradas, M.; Henriques-Pons, A.; Araújo-Jorge, T.C.; Di Virgilio, F.; Coutinho-Silva, R.; Persechini, P.M. Extracellular ATP induces cell death in CD4+/CD8+ double-positive thymocytes in mice infected with Trypanosoma cruzi. Microbes Infect.,  2003, 5(15), 1363-1371.
[http://dx.doi.org/10.1016/j.micinf.2003.09.017] [PMID: 14670449] 
[14] 
Di Virgilio, F.; Ceruti, S.; Bramanti, P.; Abbracchio, M.P. Purinergic signalling in inflammation of the central nervous system. Trends Neurosci.,  2009, 32(2), 79-87.
[http://dx.doi.org/10.1016/j.tins.2008.11.003] [PMID: 19135728] 
[15] 
Leite, P.M.; Gomes, R.S.; Figueiredo, A.B.; Serafim, T.D.; Tafuri, W.L.; de Souza, C.C.; Moura, S.A.L.; Fietto, J.L.R.; Melo, M.N.; Ribeiro-Dias, F.; Oliveira, M.A.P.; Rabello, A.; Afonso, L.C.C. Ecto-nucleotidase activities of promastigotes from Leishmania (Viannia) braziliensis relates to parasite infectivity and disease clinical outcome. PLoS Negl. Trop. Dis.,  2012, 6(10)e1850
[http://dx.doi.org/10.1371/journal.pntd.0001850] [PMID: 23071853] 
[16] 
Porcino, G.N.; Carvalho-Campos, C.; Maia, A.C.R.G.; Detoni, M.L.; Faria-Pinto, P.; Coimbra, E.S.; Marques, M.J.; Juliano, M.A.; Juliano, L.; Diniz, V.Á.; Corte-Real, S.; Vasconcelos, E.G. Leishmania (Viannia) braziliensis nucleoside triphosphate diphosphohydrolase (NTPDase 1): localization and in vitro inhibition of promastigotes growth by polyclonal antibodies. Exp. Parasitol.,  2012, 132(2), 293-299.
[http://dx.doi.org/10.1016/j.exppara.2012.08.009] [PMID: 22921497] 
[17] 
Gomes, M.T.; Lopes, A.H.; Meyer-Fernandes, J.R. Possible roles of ectophosphatases in host-parasite interactions. J. Parasitol. Res.,  2011, 2011479146
[http://dx.doi.org/10.1155/2011/479146] [PMID: 21603194] 
[18] 
Sansom, F.M. The role of the NTPDase enzyme family in parasites: what do we know, and where to from here? Parasitology,  2012, 139(8), 963-980.
[http://dx.doi.org/10.1017/S003118201200025X] [PMID: 22423612] 
[19] 
Meyer-Fernandes, J.R.; Dutra, P.M.L.; Rodrigues, C.O.; Saad-Nehme, J.; Lopes, A.H.C.S. Mg-dependent ecto-ATPase activity in Leishmania tropica. Arch. Biochem. Biophys.,  1997, 341(1), 40-46.
[http://dx.doi.org/10.1006/abbi.1997.9933] [PMID: 9143351] 
[20] 
Berrêdo-Pinho, M.; Peres-Sampaio, C.E.; Chrispim, P.P.M.; Belmont-Firpo, R.; Lemos, A.P.; Martiny, A.; Vannier-Santos, M.A.; Meyer-Fernandes, J.R. A Mg-dependent ecto-ATPase in Leishmania amazonensis and its possible role in adenosine acquisition and virulence. Arch. Biochem. Biophys.,  2001, 391(1), 16-24.
[http://dx.doi.org/10.1006/abbi.2001.2384] [PMID: 11414680] 
[21] 
Pinheiro, C.M.; Martins-Duarte, E.S.; Ferraro, R.B.; Fonseca de Souza, A.L.; Gomes, M.T.; Lopes, A.H.C.S.; Vannier-Santos, M.A.; Santos, A.L.S.; Meyer-Fernandes, J.R. Leishmania amazonensis: Biological and biochemical characterization of ecto-nucleoside triphosphate diphosphohydrolase activities. Exp. Parasitol.,  2006, 114(1), 16-25.
[http://dx.doi.org/10.1016/j.exppara.2006.02.007] [PMID: 16603157] 
[22] 
de Almeida Marques-da-Silva, E.; de Oliveira, J.C.; Figueiredo, A.B.; de Souza Lima Júnior, D.; Carneiro, C.M.; Rangel Fietto, J.L.; Crocco Afonso, L.C. Extracellular nucleotide metabolism in Leishmania: influence of adenosine in the establishment of infection. Microbes Infect.,  2008, 10(8), 850-857.
[http://dx.doi.org/10.1016/j.micinf.2008.04.016] [PMID: 18656412] 
[23] 
Maia, A.C.R.G.; Porcino, G.N.; Detoni, M. de L.; Emídio, N.B.; Marconato, D.G.; Faria-Pinto, P.; Fessel, M.R.; Reis, A.B.; Juliano, L.; Juliano, M.A.; Marques, M.J.; Vasconcelos, E.G. An antigenic domain within a catalytically active Leishmania infantum nucleoside triphosphate diphosphohydrolase (NTPDase 1) is a target of inhibitory antibodies. Parasitol. Int.,  2013, 62(1), 44-52.
[http://dx.doi.org/10.1016/j.parint.2012.09.004] [PMID: 22995148] 
[24] 
Bisaggio, D.F.R.; Peres-Sampaio, C.E.; Meyer-Fernandes, J.R.; Souto-Padrón, T. Ecto-ATPase activity on the surface of Trypanosoma cruzi and its possible role in the parasite-host cell interaction. Parasitol. Res.,  2003, 91(4), 273-282.
[http://dx.doi.org/10.1007/s00436-003-0965-8] [PMID: 14574556] 
[25] 
Meyer-Fernandes, J.R.; Saad-Nehme, J.; Peres-Sampaio, C.E.; Belmont-Firpo, R.; Bisaggio, D.F.R.; Do Couto, L.C.; Fonseca De Souza, A.L.; Lopes, A.H.S.C.; Souto-Padrón, T. A Mg-dependent ecto-ATPase is increased in the infective stages of Trypanosoma cruzi. Parasitol. Res.,  2004, 93(1), 41-50.
[http://dx.doi.org/10.1007/s00436-003-1066-4] [PMID: 15060823] 
[26] 
Santos, R.F.; Pôssa, M.A.S.; Bastos, M.S.; Guedes, P.M.M.; Almeida, M.R.; Demarco, R.; Verjovski-Almeida, S.; Bahia, M.T.; Fietto, J.L.R. Influence of Ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence. PLoS Negl. Trop. Dis.,  2009, 3(3)e387
[http://dx.doi.org/10.1371/journal.pntd.0000387] [PMID: 19255624] 
[27] 
Mariotini-Moura, C.; Silva e Bastos, M.; de Castro, F.F.; Trindade, M.L. Vasconcellos, Rde.S.; Neves-do-Valle, M.A.A.; Moreira, B.P.; Santos, Rde.F.; de Oliveira, C.M.; Cunha, L.C.S.; Souto, X.M.; Bressan, G.C.; Silva-Júnior, A.; Baqui, M.M.A.; Bahia, M.T.; de Almeida, M.R.; Meyer-Fernandes, J.R.; Fietto, J.L.R. Trypanosoma cruzi nucleoside triphosphate diphosphohydrolase 1 (TcNTPDase-1) biochemical characterization, immunolocalization and possible role in host cell adhesion. Acta Trop.,  2014, 130(1), 140-147.
[http://dx.doi.org/10.1016/j.actatropica.2013.11.008] [PMID: 24269744] 
[28] 
Fonseca, F.V.; Fonseca de Souza, A.L.; Mariano, A.C.; Entringer, P.F.; Gondim, K.C.; Meyer-Fernandes, J.R. Trypanosoma rangeli: characterization of a Mg-dependent ecto ATP-diphosphohydrolase activity. Exp. Parasitol.,  2006, 112(2), 76-84.
[http://dx.doi.org/10.1016/j.exppara.2005.09.005] [PMID: 16289087] 
[29] 
de Souza Leite, M.; Thomaz, R.; Fonseca, F.V.; Panizzutti, R.; Vercesi, A.E.; Meyer-Fernandes, J.R. Trypanosoma brucei brucei: biochemical characterization of ecto-nucleoside triphosphate diphosphohydrolase activities. Exp. Parasitol.,  2007, 115(4), 315-323.
[http://dx.doi.org/10.1016/j.exppara.2006.09.002] [PMID: 17141762] 
[30] 
Trager, W. The kinetoplast and differentiation in certain parasitic protozoa. Am. Nat.,  1965, 99(907), 255-266.
[http://dx.doi.org/10.1086/282371] 
[31] 
Stuart, K.; Brun, R.; Croft, S.; Fairlamb, A.; Gürtler, R.E.; McKerrow, J.; Reed, S.; Tarleton, R. Kinetoplastids: related protozoan pathogens, different diseases. J. Clin. Invest.,  2008, 118(4), 1301-1310.
[http://dx.doi.org/10.1172/JCI33945] [PMID: 18382742] 
[32] 
World Health Organization. Leishmaniasis, 2019. Available from: http://Www.Who.Int/Leishmaniasis/En/
[33] 
Coura, J.R. The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions--a comprehensive review. Mem. Inst. Oswaldo Cruz,  2015, 110(3), 277-282.
[http://dx.doi.org/10.1590/0074-0276140362] [PMID: 25466622] 
[34] 
Bern, C. Chagas’ disease. N. Engl. J. Med.,  2015, 373(5), 456-466.
[35] 
Dias, J.C. The indeterminate form of human chronic Chagas’ disease A clinical epidemiological review. Rev. Soc. Bras. Med. Trop.,  1989, 22(3), 147-156.
[http://dx.doi.org/10.1590/S0037-86821989000300007] [PMID: 2486527] 
[36] 
Molyneux, D.H.; Dean, L.; Adekeye, O.; Stothard, J.R.; Theobald, S. The changing global landscape of health and disease: addressing challenges and opportunities for sustaining progress towards control and elimination of neglected tropical diseases (NTDs). Parasitology,  2018, 145(13), 1647-1654.
[37] 
Akbari, M.; Oryan, A.; Hatam, G. Application of nanotechnology in treatment of leishmaniasis: A Review. Acta Trop.,  2017, 172(April), 86-90.
[http://dx.doi.org/10.1016/j.actatropica.2017.04.029] [PMID: 28460833] 
[38] 
Handler, M.Z.; Patel, P.A.; Kapila, R.; Al-Qubati, Y.; Schwartz, R.A. Cutaneous and mucocutaneous leishmaniasis: Differential
    diagnosis, diagnosis, histopathology, and management. J. Am. Acad. Dermatol.,  2015, 73(6), 911-926-927-928.
[http://dx.doi.org/10.1016/j.jaad.2014.09.014] [PMID: 26568336] 
[39] 
Goupil, L.S.; McKerrow, J.H. Introduction: drug discovery and development for neglected diseases. Chem. Rev.,  2014, 114(22), 11131-11137.
[http://dx.doi.org/10.1021/cr500546h] [PMID: 26721412] 
[40] 
Rajasekaran, R.; Chen, Y.P.P. Potential therapeutic targets and the role of technology in developing novel antileishmanial drugs. Drug Discov. Today,  2015, 20(8), 958-968.
[41] 
Saqib, M.; Ali Bhatti, A.S.; Ahmad, N.M.; Ahmed, N.; Shahnaz, G.; Lebaz, N.; Elaissari, A. Amphotericin b loaded polymeric nanoparticles for treatment of leishmania infections. Nanomaterials (Basel),  2020, 10(6)E1152
[http://dx.doi.org/10.3390/nano10061152] [PMID: 32545473] 
[42] 
Croft, S.L.; Barrett, M.P.; Urbina, J.A. Chemotherapy of trypanosomiases and leishmaniasis. Trends Parasitol.,  2005, 21(11), 508-512.
[http://dx.doi.org/10.1016/j.pt.2005.08.026] [PMID: 16150644] 
[43] 
Mitropoulos, P.; Konidas, P.; Durkin-Konidas, M. New World cutaneous leishmaniasis: updated review of current and future diagnosis and treatment. J. Am. Acad. Dermatol.,  2010, 63(2), 309-322.
[http://dx.doi.org/10.1016/j.jaad.2009.06.088] [PMID: 20303613] 
[44] 
Carneiro, G.; Aguiar, M.G.; Fernandes, A.P.; Ferreira, L.A.M. Drug delivery systems for the topical treatment of cutaneous leishmaniasis. Expert Opin. Drug Deliv.,  2012, 9(9), 1083-1097.
[http://dx.doi.org/10.1517/17425247.2012.701204] [PMID: 22724539] 
[45] 
Ramesh, V.; Dixit, K.K.; Sharma, N.; Singh, R.; Salotra, P. Assessing the efficacy and safety of liposomal amphotericin b and
    miltefosine in combination for treatment of post kala-azar dermal
    leishmaniasis. J. Infect. Dis.,  2020, 221(4), 608-617.
[http://dx.doi.org/10.1093/infdis/jiz486] [PMID: 31854451] 
[46] 
Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M.; den Boer, M.; Davidson, R.N.; Figueras, C.; Gradoni, L.; Kafetzis, D.A.; Ritmeijer, K.; Rosenthal, E.; Royce, C.; Russo, R.; Sundar, S.; Alvar, J. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin. Infect. Dis.,  2006, 43(7), 917-924.
[http://dx.doi.org/10.1086/507530] [PMID: 16941377] 
[47] 
Kapil, S.; Singh, P.K.; Silakari, O. An update on small molecule strategies targeting leishmaniasis. Eur. J. Med. Chem.,  2018, 157, 339-367.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.012] [PMID: 30099256] 
[48] 
Santos, S.S.; de Araújo, R.V.; Giarolla, J.; Seoud, O.E.; Ferreira, E.I. Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. Int. J. Antimicrob. Agents,  2020, 55(4)105906
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105906] [PMID: 31987883] 
[49] 
Khan, W.; Kumar, N. Drug targeting to macrophages using paromomycin-loaded albumin microspheres for treatment of visceral leishmaniasis: an in vitro evaluation. J. Drug Target.,  2011, 19(4), 239-250.
[http://dx.doi.org/10.3109/1061186X.2010.492524] [PMID: 20545446] 
[50] 
Hendrickx, S.; Van Bockstal, L.; Bulté, D.; Mondelaers, A.; Aslan, H.; Rivas, L.; Maes, L.; Caljon, G. Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection. Parasit. Vectors,  2020, 13(1), 96.
[http://dx.doi.org/10.1186/s13071-020-3972-z] [PMID: 32087758] 
[51] 
Bhattacharya, S.K.; Sinha, P.K.; Sundar, S.; Thakur, C.P.; Jha, T.K.; Pandey, K.; Das, V.R.; Kumar, N.; Lal, C.; Verma, N.; Singh, V.P.; Ranjan, A.; Verma, R.B.; Anders, G.; Sindermann, H.; Ganguly, N.K. Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J. Infect. Dis.,  2007, 196(4), 591-598.
[http://dx.doi.org/10.1086/519690] [PMID: 17624846] 
[52] 
Andrade, H.M.; Toledo, V.P.C.P.; Pinheiro, M.B.; Guimarães, T.M.P.D.; Oliveira, N.C.; Castro, J.A.; Silva, R.N.; Amorim, A.C.; Brandão, R.M.S.S.; Yoko, M.; Silva, A.S.; Dumont, K.; Ribeiro, M.L., Jr; Bartchewsky, W.; Monte, S.J.H. Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (=L. chagasi) in Brazil. Vet. Parasitol.,  2011, 181(2-4), 83-90.
[http://dx.doi.org/10.1016/j.vetpar.2011.05.009] [PMID: 21641721] 
[53] 
Bastos, M.S.; Tremblay, A.; Agripino, J.M.; Rabelo, I.L.A.; Barreto, L.P.; Pelletier, J.; Lecka, J.; Silva-Júnior, A.; Bressan, G.C.; Almeida, M.R.; Sévigny, J.; Fietto, J.L.R. The expression of NTPDase1 and -2 of Leishmania infantum chagasi in bacterial and mammalian cells: Comparative expression, refolding and nucleotidase characterization. Protein Expr. Purif.,  2017, 131, 60-69.
[http://dx.doi.org/10.1016/j.pep.2016.11.004] [PMID: 27856402] 
[54] 
Vijayamahantesh; Amit, A.; Dikhit, M. R.; Mishra, A.; Singh, A.
    K.; Das, V. N. R.; Das, P.; Bimal, S. Adenosine generated by
    ectonucleotidases modulates the host immune system during
    visceral leishmaniasis. Cytokine,  2017, 91(April), 170-179.
[http://dx.doi.org/10.1016/j.cyto.2017.01.001] 
[55] 
Chaves, S.P.; Torres-Santos, E.C.; Marques, C.; Figliuolo, V.R.; Persechini, P.M.; Coutinho-Silva, R.; Rossi-Bergmann, B. Modulation of P2X(7) purinergic receptor in macrophages by Leishmania amazonensis and its role in parasite elimination. Microbes Infect.,  2009, 11(10-11), 842-849.
[http://dx.doi.org/10.1016/j.micinf.2009.05.001] [PMID: 19439191] 
[56] 
Detoni, M.L.; Fessel, M.R.; Maia, A.C.R.G.; Porcino, G.N.; Quellis, L.R.; Faria-Pinto, P.; Marques, M.J.; Juliano, M.A.; Juliano, L.; Diniz, V.A.; Côrte-Real, S.; Gonçalves-da-Costa, S.C.; Souza, C.S.F.; Vasconcelos, E.G. An antigenic domain of the Leishmania amazonensis nucleoside triphosphate diphosphohydrolase (NTPDase 1) is associated with disease progression in susceptible infected mice. Parasitol. Res.,  2013, 112(8), 2773-2782.
[http://dx.doi.org/10.1007/s00436-013-3445-9] [PMID: 23681191] 
[57] 
Lima, M.H.F.; Sacramento, L.A.; Quirino, G.F.S.; Ferreira, M.D.; Benevides, L.; Santana, A.K.M.; Cunha, F.Q.; Almeida, R.P.; Silva, J.S.; Carregaro, V. Leishmania infantum parasites subvert the host inflammatory response through the adenosine a2a receptor to promote the establishment of infection. Front. Immunol.,  2017, 8(JUL), 815.
[http://dx.doi.org/10.3389/fimmu.2017.00815] [PMID: 28775724] 
[58] 
Maioli, T.U.; Takane, E.; Arantes, R.M.E.; Fietto, J.L.R.; Afonso, L.C.C. Immune response induced by new world leishmania species in c57bl/6 mice. Parasitol. Res.,  2004, 94(3), 207-212.
[http://dx.doi.org/10.1007/s00436-004-1193-6] [PMID: 15378352] 
[59] 
Rezende-Soares, F.A.; Carvalho-Campos, C.; Marques, M.J.; Porcino, G.N.; Giarola, N.L.L.; Costa, B.L.S.; Taunay-Rodrigues, A.; Faria-Pinto, P.; Souza, M.A.; Diniz, V.A.; Corte-Real, S.; Juliano, M.A.; Juliano, L.; Vasconcelos, E.G. Cytochemical localization of ATP diphosphohydrolase from Leishmania (Viannia) braziliensis promastigotes and identification of an antigenic and catalytically active isoform. Parasitology,  2010, 137(5), 773-783.
[http://dx.doi.org/10.1017/S0031182009991661] [PMID: 19961654] 
[60] 
Maia, A.C.R.G.; Detoni, M.L.; Porcino, G.N.; Soares, T.V.; do Nascimento Gusmão, M.A.; Fessel, M.R.; Marques, M.J.; Souza, M.A.; Coelho, P.M.Z.; Estanislau, J.A.S.G.; da Costa Rocha, M.O.; de Oliveira Santos, M.; Faria-Pinto, P.; Vasconcelos, E.G. Occurrence of a conserved domain in ATP diphosphohydrolases from pathogenic organisms associated to antigenicity in human parasitic diseases. Dev. Comp. Immunol.,  2011, 35(10), 1059-1067.
[http://dx.doi.org/10.1016/j.dci.2011.03.026] [PMID: 21527274] 
[61] 
Faria-Pinto, P.; Rezende-Soares, F.A.; Molica, A.M.; Montesano, M.A.; Marques, M.J.; Rocha, M.O.C.; Gomes, J.A.S.; Enk, M.J.; Correa-Oliveira, R.; Coelho, P.M.Z.; Neto, S.M.; Franco, O.L.; Vasconcelos, E.G. Mapping of the conserved antigenic domains shared between potato apyrase and parasite ATP diphosphohydrolases: potential application in human parasitic diseases. Parasitology,  2008, 135(8), 943-953.
[http://dx.doi.org/10.1017/S0031182008004538] [PMID: 18598576] 
[62] 
Mendes, R.G.P.R.; Gusmão, M.A.; Maia, A.C. Detoni, Mde.L.;
    Porcino, G.N.; Soares, T.V.; Juliano, M.A.; Juliano, L.; Coelho,
    P.M.; Lenzi, H.L.; Faria-Pinto, P.; Vasconcelos, E.G.
    Immunostimulatory property of a synthetic peptide belonging to the
    soluble ATP diphosphohydrolase isoform (SmATPDase 2) and
    immunolocalisation of this protein in the Schistosoma mansoni egg. Mem. Inst. Oswaldo Cruz,  2011, 106(7), 808-813.
[http://dx.doi.org/10.1590/S0074-02762011000700005] [PMID: 22124552] 
[63] 
Ivens, A. C.; Peacock, C. S.; Worthey, E. A.; Murphy, L.; Aggarwal, G.; Berriman, M.; Sisk, E.; Rajandream, M. A.; Adlem, E.; Aert, R.; Anupama, A.; Apostolou, Z.; Attipoe, P.; Bason, N.; Bauser, C.; Beck, A.; Beverley, S. M.; Bianchettin, G.; Borzym, K.; Bothe, G.; Bruschi, C. V; Collins, M.; Cadag, E.; Ciarloni, L.; Clayton, C.; Coulson, R. M. R.; Cronin, A.; Cruz, A. K.; Davies, R. M.; De Gaudenzi, J.; Dobson, D. E.; Duesterhoeft, A.; Fazelina, G.; Fosker, N.; Frasch, A. C.; Fraser, A.; Fuchs, M.; Gabel, C.; Goble, A.; Goffeau, A.; Harris, D.; Hertz-Fowler, C.; Hilbert, H.; Horn, D.; Huang, Y.; Klages, S.; Knights, A.; Kube, M.; Larke, N.; Litvin, L.; Lord, A.; Louie, T.; Marra, M.; Masuy, D.; Matthews, K.; Michaeli, S.; Mottram, J. C.; Müller-Auer, S.; Munden, H.; Nelson, S.; Norbertczak, H.; Oliver, K.; O’Neil, S.; Pentony, M.; Pohl, T. M.; Price, C.; Purnelle, B.; Quail, M. A.; Rabbinowitsch, E.; Reinhardt, R.; Rieger, M.; Rinta, J.; Robben, J.; Robertson, L.; Ruiz, J. C.; Rutter, S.; Saunders, D.; Schäfer, M.; Schein, J.; Schwartz, D. C.; Seeger, K.; Seyler, A.; Sharp, S.; Shin, H.; Sivam, D.; Squares, R.; Squares, S.; Tosato, V.; Vogt, C.; Volckaert, G.; Wambutt, R.; Warren, T.; Wedler, H.; Woodward, J.; Zhou, S.; Zimmermann, W.; Smith, D. F.; Blackwell, J. M.; Stuart, K. D.; Barrell, B.; Myler, P. J. The genome of the kinetoplastid parasite, leishmania major. Science (80-. ),  2005, 309(5733), 436-442.
[64] 
Vijayamahantesh, V. Tinkering with targeting nucleotide signaling for control of intracellular leishmania parasites. Cytokine,  2018, 2019(119), 129-143.
[http://dx.doi.org/10.1016/j.cyto.2019.03.005] 
[65] 
Kukulski, F.; Lévesque, S.A.; Sévigny, J. Impact of ectoenzymes on p2 and p1 receptor signaling.In: Advances in Pharmacology;
    Academic Press Inc.: Cambridge , 2011; 61, pp. 263-299.
[http://dx.doi.org/10.1016/B978-0-12-385526-8.00009-6] 
[66] 
Savio, L.E.B.; Coutinho-Silva, R. Immunomodulatory effects of P2X7 receptor in intracellular parasite infections. Curr. Opin. Pharmacol.,  2019, 47, 53-58.
[http://dx.doi.org/10.1016/j.coph.2019.02.005] [PMID: 30901737] 
[67] 
Coutinho-Silva, R.; Ojcius, D.M. Role of extracellular nucleotides in the immune response against intracellular bacteria and protozoan parasites. Microbes Infect.,  2012, 14(14), 1271-1277.
[http://dx.doi.org/10.1016/j.micinf.2012.05.009] [PMID: 22634346] 
[68] 
Savio, L.E.B.; de Andrade Mello, P.; da Silva, C.G.; Coutinho-Silva, R. The P2X7 receptor in inflammatory diseases: angel or demon? Front. Pharmacol.,  2018, 9(FEB), 52.
[http://dx.doi.org/10.3389/fphar.2018.00052] [PMID: 29467654] 
[69] 
Figliuolo, V.R.; Chaves, S.P.; Savio, L.E.B.; Thorstenberg, M.L.P.; Machado Salles, É.; Takiya, C.M.; D’Império-Lima, M.R.; de Matos Guedes, H.L.; Rossi-Bergmann, B.; Coutinho-Silva, R. The role of the P2X7 receptor in murine cutaneous leishmaniasis: aspects of inflammation and parasite control. Purinergic Signal.,  2017, 13(2), 143-152.
[http://dx.doi.org/10.1007/s11302-016-9544-1] [PMID: 27866341] 
[70] 
Silva-Gomes, N.L.; Ennes-Vidal, V.; Carolo, J.C.F.; Batista, M.M.; Soeiro, M.N.; Menna-Barreto, R.; Moreira, O.C. Nucleoside triphosphate diphosphohydrolase1 (TcNTPDase-1) gene expression is increased due to heat shock and in infective forms of Trypanosoma cruzi. Parasit. Vectors,  2014, 7(1), 463.
[http://dx.doi.org/10.1186/s13071-014-0463-0] [PMID: 25287580] 
[71] 
Moreira-Souza, A.C.A.; Almeida-da-Silva, C.L.C.; Rangel, T.P.; Rocha, G.D.C.; Bellio, M.; Zamboni, D.S.; Vommaro, R.C.; Coutinho-Silva, R. The P2X7 receptor mediates toxoplasma gondii control in macrophages through canonical nlrp3 inflammasome activation and reactive oxygen species production. Front. Immunol.,  2017, 8(OCT), 1257.
[http://dx.doi.org/10.3389/fimmu.2017.01257] [PMID: 29075257] 
[72] 
Meuser-Batista, M.; Corrêa, J.R.; Carvalho, V.F.; de Carvalho Britto, C.F.D.P.; Moreira, O.C.; Batista, M.M.; Soares, M.J.; Filho, F.A.F.; Silva, E. P.M.; Lannes-Vieira, J.; Silva, R.C.; Henriques-Pons, A. Mast cell function and death in Trypanosoma cruzi infection. Am. J. Pathol.,  2011, 179(4), 1894-1904.
[http://dx.doi.org/10.1016/j.ajpath.2011.06.014] [PMID: 21819958] 
[73] 
Marques-da-Silva, C.; Chaves, M.M.; Rodrigues, J.C.; Corte-Real, S.; Coutinho-Silva, R.; Persechini, P.M. Differential modulation of ATP-induced P2X7-associated permeabilities to cations and anions of macrophages by infection with Leishmania amazonensis. PLoS One,  2011, 6(9)e25356
[http://dx.doi.org/10.1371/journal.pone.0025356] [PMID: 21966508] 
[74] 
Abbracchio, M.P.; Ceruti, S. P1 receptors and cytokine secretion. Purinergic Signal.,  2007, 3(1-2), 13-25.
[http://dx.doi.org/10.1007/s11302-006-9033-z] [PMID: 18404415] 
[75] 
Fredholm, B.B.; Irenius, E.; Kull, B.; Schulte, G. Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. Biochem. Pharmacol.,  2001, 61(4), 443-448.
[http://dx.doi.org/10.1016/S0006-2952(00)00570-0] [PMID: 11226378] 
[76] 
Vijayamahantesh; Amit, A.; Dikhit, M.R.; Singh, A.K.; Venkateshwaran, T.; Das, V.N.R.; Das, P.; Bimal, S. Immuno-informatics based approaches to identify CD8+ T cell epitopes within the Leishmania donovani 3-ectonucleotidase in cured visceral leishmaniasis subjects. Microbes Infect.,  2017, 19(6), 358-369.
[http://dx.doi.org/10.1016/j.micinf.2017.03.002] [PMID: 28373107] 
[77] 
Vijayamahantesh; Amit, A.; Kumar, S.; Dikhit, M. R.; Jha, P. K.;
    Singh, A. K.; Sinha, K. K.; Pandey, K.; Das, V. N. R.; Das, P.;
    Bimal, S. Up regulation of a2b adenosine receptor on monocytes
    are crucially required for immune pathogenicity in indian patients
    exposed to leishmania donovani. Cytokine,  2016, 79, 38-44.
[http://dx.doi.org/10.1016/j.cyto.2015.12.016] 
[78] 
Corriden, R.; Insel, P.A. New insights regarding the regulation of chemotaxis by nucleotides, adenosine, and their receptors. Purinergic Signal.,  2012, 8(3), 587-598.
[http://dx.doi.org/10.1007/s11302-012-9311-x] [PMID: 22528684] 
[79] 
Kronlage, M.; Song, J.; Sorokin, L.; Isfort, K.; Schwerdtle, T.; Leipziger, J.; Robaye, B.; Conley, P.B.; Kim, H.C.; Sargin, S.; Schön, P.; Schwab, A.; Hanley, P.J. Autocrine purinergic receptor signaling is essential for macrophage chemotaxis. Sci. Signal.,  2010, 3(132), ra55.
[http://dx.doi.org/10.1126/scisignal.2000588] [PMID: 20664064] 
[80] 
Csóka, B.; Selmeczy, Z.; Koscsó, B.; Németh, Z.H.; Pacher, P.; Murray, P.J.; Kepka-Lenhart, D.; Morris, S.M., Jr; Gause, W.C.; Leibovich, S.J.; Haskó, G. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J.,  2012, 26(1), 376-386.
[http://dx.doi.org/10.1096/fj.11-190934] [PMID: 21926236] 
[81] 
Lambrecht, G.; Braun, K.; Damer, M.; Ganso, M.; Hildebrandt, C.; Ullmann, H.; Kassack, M.U.; Nickel, P. Structure-activity relationships of suramin and pyridoxal-5′-phosphate derivatives as P2 receptor antagonists. Curr. Pharm. Des.,  2002, 8(26), 2371-2399.
[http://dx.doi.org/10.2174/1381612023392973] [PMID: 12369951] 
[82] 
Novaes, R.D.; Santos, E.C.; Cupertino, M.C.; Bastos, D.S.S.; Mendonça, A.A.S.; Marques-da-Silva, E.A.; Cardoso, S.A.; Fietto, J.L.R.; Oliveira, L.L. Purinergic antagonist suramin aggravates myocarditis and increases mortality by enhancing parasitism, inflammation, and reactive tissue damage in trypanosoma cruzi-infected mice. Oxid. Med. Cell. Longev.,  2018, 20187385639
[http://dx.doi.org/10.1155/2018/7385639] [PMID: 30364017] 
[83] 
Coutinho-Silva, R.; Monteiro da Cruz, C.; Persechini, P.M.; Ojcius, D.M. The role of P2 receptors in controlling infections by intracellular pathogens. Purinergic Signal.,  2007, 3(1-2), 83-90.
[http://dx.doi.org/10.1007/s11302-006-9039-6] [PMID: 18404421] 
[84] 
Cascabulho, C.M.; Menna-Barreto, R.F.S.; Coutinho-Silva, R.; Persechini, P.M.; Henriques-Pons, A. P2X7 modulatory web in trypanosoma cruzi infection. Parasitol. Res.,  2008, 103(4), 829-838.
[http://dx.doi.org/10.1007/s00436-008-1063-8] [PMID: 18604654] 
[85] 
Sierra, H.; Cordova, M.; Chen, C.J.; Rajadhyaksha, M. Confocal
    imaging-guided laser ablation of basal cell carcinomas: an ex vivo
    study. J Invest Dermatol.,  2015, 135(2), 612-615.
[http://dx.doi.org/10.1038/jid.2014.371] 
[86] 
Souza, V.D.; Dos Santos, J.T.; Cabral, F.L.; Barbisan, F.; Azevedo, M.I.; Dias Carli, L.F.; de Avila Botton, S.; Dos Santos Jaques, J.A.; Rosa Leal, D.B. Evaluation of P2X7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of Chagas disease. Microb. Pathog.,  2017, 104, 32-38.
[http://dx.doi.org/10.1016/j.micpath.2017.01.002] [PMID: 28062289] 
[87] 
Pérez-Molina, J.A.; Molina, I. Chagas disease. The Lancet,  2018, 391(10115), 82-94.
[88] 
Fernández-Robledo, J.A.; Vasta, G.R. Production of recombinant proteins from protozoan parasites. Trends Parasitol.,  2010, 26(5), 244-254.
[http://dx.doi.org/10.1016/j.pt.2010.02.004] [PMID: 20189877] 
[89] 
de Souza, R.F.; Dos Santos, Y.L.; de Souza Vasconcellos, R.; Borges-Pereira, L.; Caldas, I.S.; de Almeida, M.R.; Bahia, M.T.; Fietto, J.L.R. Recombinant leishmania (leishmania) infantum ecto-nucleoside triphosphate diphosphohydrolase NTPDase-2 as a new antigen in canine visceral leishmaniasis diagnosis. Acta Trop.,  2013, 125(1), 60-66.
[http://dx.doi.org/10.1016/j.actatropica.2012.09.011] [PMID: 23022017] 
[90] 
Zóboli, A.P.C.; Fietto, J.L.R.; Lamêgo, M.R. de A.; DeSouza, R.F. Recombinant E-ntpdases, use in the production of diagnostic kit for
    detection of antibodies in leishmaniasis caused by species of the
    genus leishmania, WO2011153602A2, 2012.
[91] 
Tan, F.; Hu, X.; Pan, C.W.; Ding, J.Q.; Chen, X.G. Monoclonal antibodies against nucleoside triphosphate hydrolase-II can reduce the replication of Toxoplasma gondii. Parasitol. Int.,  2010, 59(2), 141-146.
[http://dx.doi.org/10.1016/j.parint.2009.12.007] [PMID: 20056166] 
[92] 
Khan, C.M.A.; Villarreal-Ramos, B.; Pierce, R.J.; Riveau, G.; Demarco de Hormaeche, R.; McNeill, H.; Ali, T.; Fairweather, N.; Chatfield, S.; Capron, A.; Dougan, G.; Hormaeche, C.E. Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella. Proc. Natl. Acad. Sci. USA,  1994, 91(23), 11261-11265.
[http://dx.doi.org/10.1073/pnas.91.23.11261] [PMID: 7972044] 
Rights & Permissions Print Cite
Article Metrics
27
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1568026620666201005125146	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

ENTPDases from Pathogenic Trypanosomatids and Purinergic Signaling: Shedding Light towards Biotechnological Applications

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
