Trypanosoma cruzi: analysis of two different strains after piplartine treatment

Abstract

The hemoflagellate protozoan, Trypanosoma cruzi, mainly transmitted by triatomine insects through blood transfusion or from mother-to-child, causes Chagas' disease. This is a serious parasitic disease that occurs in Latin America, with considerable social and economic impact. Nifurtimox and benznidazole, drugs indicated for treating infected persons, are effective in the acute phase, but poorly effective during the chronic phase. Therefore, it is extremely urgent to find innovative chemotherapeutic agents and/or effective vaccines. Since piplartine has several biological activities, including trypanocidal activity, the present study aimed to evaluate it on two T. cruzi strains proteome. Considerable changes in the expression of some important enzymes involved in parasite protection against oxidative stress, such as tryparedoxin peroxidase (TXNPx) and methionine sulfoxide reductase (MSR) was observed in both strains. These findings suggest that blocking the expression of the two enzymes could be potential targets for therapeutic studies.

The Role of Methionine Sulfoxide Reductases in Oxidative Stress Tolerance and Virulence of Staphylococcus aureus and Other Bacteria

“…Similar to S. aureus MSRA1 / MSRB , in H. pylori [ 20 ], E. coli [ 28 ], and B. subtilis [ 29 ] the late log and stationary phase cultures of these bacteria had the highest MSR activity. In addition to MSRA1 / MSRB induction by cell wall-active antibiotics, piplartine, a biologically active alkaloid from peppers [ 30 ], showed enhanced MSR expression in the pathogenic parasite, Trypanosoma cruzi [ 31 ].…”

In Vitro Phenotypic Activity and In Silico Analysis of Natural Products from Brazilian Biodiversity on Trypanosoma cruzi

“…The piplartine isolated from P. tuberculatum displayed high activity against both intracellular and bloodstream forms of T. cruzi in vitro (EC 50 = 8.1 and 5.4 μM, respectively) corroborating previous findings reporting anti- T. cruzi activity of other biomolecules isolated from different Piper species. According to Vieira et al (2018) [ 31 ], piplartine may induce an imbalance of enzymes related to redox metabolism in some trypanosomes, due to the oxidation process of several amino acid residues. Likewise, other natural metabolites found in Piper species, such as the volatile monoterpene [ 32 ] linalool (one of the main constituents of an essential oil of P. aduncum) , showed an outstanding effect against cell-derived trypomastigotes (EC 50 = 0.31 μg/mL), although still with a limited selectivity index of 2.9 [ 33 ].…”

Precision Health for Chagas Disease: Integrating Parasite and Host Factors to Predict Outcome of Infection and Response to Therapy

“…The differential resistance of T. cruzi to BNZ among isolates has been documented (Bustamante et al, 2014;Abegg et al, 2017;Vieira et al, 2018). This intrinsic resistance in some strains could explain why some patients receiving the same BNZ treatment show parasitological cure while others do not.…”