TcI isolates of Trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice

María Paola Zago, Yashoda Hosakote Madaiah, Sue jie Koo, Monisha Dhiman, María Dolores Piñeyro, Adriana Parodi-Talice, Miguel A. Basombrio, Carlos Robello, Nisha J. Gargc

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Abstract

Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana (COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity (TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/ matrix-assisted laser desorption ionization-time of flight mass spectrometry, followed by functional annotation of the differential proteome data sets (≥2-fold change, P<0.05), showed that several proteins involved in (i) cytoskeletal assembly and remodeling, essential for flagellar wave frequency and amplitude and forward motility of the parasite, and (ii) the parasite-specific antioxidant network were enhanced in COL and SYL (versus TCC) trypomastigotes. Western blotting confirmed the enhanced protein levels of cytosolic and mitochondrial tryparedoxin peroxidases and their substrate (tryparedoxin) and iron superoxide dismutase in COL and SYL (versus TCC) trypomastigotes. Further, COL and SYL (but not TCC) were resistant to exogenous treatment with stable oxidants (H2O2 and peroxynitrite [ONOO-]) and dampened the intracellular superoxide and nitric oxide response in macrophages, and thus these isolates escaped from macrophages. Our findings suggest that protein expression conducive to increase in motility and control of macrophage-derived free radicals provides survival and persistence benefits to TcI isolates of T. cruzi.

Original languageEnglish (US)
Pages (from-to)1842-1856
Number of pages15
JournalInfection and Immunity
Volume84
Issue number6
DOIs
StatePublished - Jun 1 2016

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Trypanosoma cruzi
Virulence
Parasitemia
Antioxidants
Macrophages
Survival
Parasites
Proteins
Peroxynitrous Acid
Tropism
Electrophoresis, Gel, Two-Dimensional
Proteome
Cardiomyopathies
Oxidants
Superoxides
Proteomics
Superoxide Dismutase
Free Radicals
Insects
Mass Spectrometry

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

TcI isolates of Trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice. / Zago, María Paola; Hosakote Madaiah, Yashoda; Koo, Sue jie; Dhiman, Monisha; Piñeyro, María Dolores; Parodi-Talice, Adriana; Basombrio, Miguel A.; Robello, Carlos; Gargc, Nisha J.

In: Infection and Immunity, Vol. 84, No. 6, 01.06.2016, p. 1842-1856.

Research output: Contribution to journalArticle

Zago, María Paola ; Hosakote Madaiah, Yashoda ; Koo, Sue jie ; Dhiman, Monisha ; Piñeyro, María Dolores ; Parodi-Talice, Adriana ; Basombrio, Miguel A. ; Robello, Carlos ; Gargc, Nisha J. / TcI isolates of Trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice. In: Infection and Immunity. 2016 ; Vol. 84, No. 6. pp. 1842-1856.
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abstract = "Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana (COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity (TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/ matrix-assisted laser desorption ionization-time of flight mass spectrometry, followed by functional annotation of the differential proteome data sets (≥2-fold change, P<0.05), showed that several proteins involved in (i) cytoskeletal assembly and remodeling, essential for flagellar wave frequency and amplitude and forward motility of the parasite, and (ii) the parasite-specific antioxidant network were enhanced in COL and SYL (versus TCC) trypomastigotes. Western blotting confirmed the enhanced protein levels of cytosolic and mitochondrial tryparedoxin peroxidases and their substrate (tryparedoxin) and iron superoxide dismutase in COL and SYL (versus TCC) trypomastigotes. Further, COL and SYL (but not TCC) were resistant to exogenous treatment with stable oxidants (H2O2 and peroxynitrite [ONOO-]) and dampened the intracellular superoxide and nitric oxide response in macrophages, and thus these isolates escaped from macrophages. Our findings suggest that protein expression conducive to increase in motility and control of macrophage-derived free radicals provides survival and persistence benefits to TcI isolates of T. cruzi.",
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AU - Zago, María Paola

AU - Hosakote Madaiah, Yashoda

AU - Koo, Sue jie

AU - Dhiman, Monisha

AU - Piñeyro, María Dolores

AU - Parodi-Talice, Adriana

AU - Basombrio, Miguel A.

AU - Robello, Carlos

AU - Gargc, Nisha J.

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