Abstract
Trypanosoma cruzi is transmitted to vertebrate hosts during the feeding of blood-sucking insects. After the invasion of host cells, the parasite resides within the parasitophorous vacuole until to escape to host cytoplasm and to proliferate, establishing an infection. Studies demonstrated that some intracellular parasites have to acquire all essential nutrients as well as transition metals from the host cell to be pathogenic, to maintain the homeostasis and to replicate. The present study investigated the progressive steps of the intracellular parasite development and establishment of infection in the presence of ZnCl2, CdCl2 and HgCl2. LLC-MK2 cells were infected with trypomastigotes during 6–84 h to investigate the steps of intracellular parasite development. After the host cells were infected during 12 h and treated with metals during 24 or 60 h or they were treated for 24 h and cultured for 72 h more to observe the reversibility. The results showed that the non-synchronous invasion of trypomastigotes resulted in an increasing number of intracellular parasites in intermediary forms (until 24 h post-infection), the appearance (from 36 h) and proliferation (84 h) of the amastigotes. The 24 h-treatments were not enough to impair parasite escape to the host cytoplasm and reproduction. However, 60 h of incubations led to a significant reduction in parasite numbers, as well as the reversibility assays. In conclusion, new insights about the intracellular T. cruzi development in the presence of metals were provided, and further studies should be performed to investigate the events involved in parasite death and elimination.
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Alvarez VE, Niemirowicz GT, Cazzulo JJ (2012) The peptidases of Trypanosoma cruzi: digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death. Biochim Biophys Acta 1824:195–206
Andrews NW, Whitlow MB (1989) Secretion by Trypanosoma cruzi of a hemolysin active at low pH. Mol Biochem Parasitol 33:249–256
Ariyanayagam MR, Fairlamb AH (2001) Ovothiol and trypanothione as antioxidants in trypanosomatids. Mol Biochem Parasitol 115:189–198
Benítez J, Becco L, Correia I et al (2011) Vanadium polypyridyl compounds as potential antiparasitic and antitumoral agents: new achievements. J Inorg Biochem 105:303–312
Caradonna KL, Engel JC, Jacobi D et al (2013) Host metabolism regulates intracellular growth of Trypanosoma cruzi. Host Cell Microbe 13:108–117
Carvalho CS, de Melo EJT, Tenorio RP, Góes AJ (2010) Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives. Braz J Med Biol Res 43:139–149
de Carvalho LP, de Melo EJT (2016) Essential and nonessential metal effects on intracellular Toxoplasma gondii. Eur J Biomed Pharm Sci 3:22–32
de Carvalho LP, de Melo EJT (2017) Life and death of Trypanosoma cruzi in presence of metals. Biometals 30:955–974
de Carvalho TMU, de Souza W (1989) Early events related with the behaviour of Trypanosoma cruzi within an endocytic vacuole in mouse peritoneal macrophages. Cell Struct Funct 14:383–392
de Carvalho LP, Gomes MAGB, Rocha BS, de Oliveira RR, de Melo EJT (2013) Anti-parasite effects of new thiosemicarbazones and their products thiazolidinone including cellular aspects of intracellular elimination of Trypanosoma cruzi in vitro. J Dev Drugs 3:1000126
de Souza W, de Carvalho TMU, Barrias ES (2010) Review on Trypanosoma cruzi: host cell interaction. Int J Cell Biol. https://doi.org/10.1155/2010/295394
Eide DJ (2006) Zinc transporters and the cellular trafficking of zinc. Biochim Biophys Acta 1763:711–722
Formigari A, Irato P, Santon A (2007) Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comp Biochem Physiol C Toxicol Pharmacol 146:443–459
Girault L, Boudou A, Drfourc EJ (1997) Methyl mercury interactions with phospholipid membranes as reported by fluorescence, 31P and 199Hg NMR. Biochim Biophys Acta 1325:250–262
Gomes MAGB, de Carvalho LP, de Melo EJT, Oliveira RR, Maria EJ (2012) Evaluating anti-Toxoplasma gondii activity of new serie of phenylsemicarbazone and phenylthiosemicarbazones in vitro. Med Chem Res 22:3574–3580
Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87
Lemire JA, Harrison JJ, Turner RJ (2013) Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11:371–384
Ley V, Robbins ES, Nussenzweig V, Andrews NW (1990) The exit of Trypanosoma cruzi from the phagosome is inhibited by raising the pH of acidic compartments. J Exp Med 171:401–413
Martinez-Finley EJ, Chakraborty S, Fretham SJB, Aschner M (2012) Cellular transport and homeostasis of essential and nonessential metals. Metallomics 4:593–605
Martins DA, Gouvea LR, da Gama JBD et al (2012) Copper(II)–fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability. Biometals 25:951–960
Maya JD, Cassels BK, Iturriaga-Vásquez P et al (2007) Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comp Biochem Physiol A Mol Integr Physiol 146:601–620
Moulis JM (2010) Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals. Biometals 23:877–896
Nardy AF, Freire-de-Lima CG, Morrot A (2015) Immune evasion strategies of Trypanosoma cruzi. J Immunol Res. https://doi.org/10.1155/2015/178947
Porcheron G, Garénaux A, Proulx J et al (2013) Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence. Front Cell Infect Microbiol 3:90
Rodriguez A, Samoff E, Rioult MG et al (1996) Host cell invasion by trypanosomes requires lysosomes and microtubule/kinesin-mediated transport. J Cell Biol 134:349–362
Santos D, Parajón-Costa B, Rossi M et al (2012) Activity on Trypanosoma cruzi, erythrocytes lysis and biologically relevant physicochemical properties of Pd(II) and Pt(II) complexes of thiosemicarbazones derived from 1-indanones. J Inorg Biochem 117:270–276
Tardieux I, Nathanson MH, Andrews NW (1994) Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients. J Exp Med 179:1017–1022
Turrens JF (2004) Oxidative stress and antioxidant defenses: a target for the treatment of diseases caused by parasitic protozoa. Mol Asp Med 25:211–220
Tyler KM, Engman DM (2001) The life cycle of Trypanosoma cruzi revisited. Int J Parasitol 31:472–481
Valko M, Leibfritz D, Moncol J et al (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84
Vieites M, Otero L, Santos D et al (2008) Platinum-based complexes of bioactive 3-(5-nitrofuryl) acroleine thiosemicarbazones showing anti-Trypanosoma cruzi activity. J Inorg Biochem 103:411–418
Weinberg ED (1966) Roles of metallic ions in host-parasite interactions differential metallic ion growth requirements of virulent and avirulent bacterial strains. Bacteriol Rev 30:136–151
Woolsey AM, Sunwoo L, Petersen CA et al (2003) Novel Pl 3- kinase-dependent mechanisms of trypanosome invasion and vacuole maturation. J Cell Sci 116:3611–3622
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FAPERJ (Fundação de Amparo à Pesquisa do Rio de Janeiro) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) (Grant No. E-26/010002612/2014).
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Lais Carvalho performed all assays while Edésio Melo organized the results and he also wrote the paper.
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Pessanha de Carvalho, L., Tenório de Melo, E.J. Intracellular development of Trypanosoma cruzi in the presence of metals. J Parasit Dis 42, 372–381 (2018). https://doi.org/10.1007/s12639-018-1010-2
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DOI: https://doi.org/10.1007/s12639-018-1010-2