Differential expression and activity of arginine kinase between the American trypanosomatids Trypanosoma rangeli and Trypanosoma cruzi

Exp Parasitol. 2021 Nov:230:108159. doi: 10.1016/j.exppara.2021.108159. Epub 2021 Sep 23.

Abstract

Trypanosoma rangeli is a non-virulent hemoflagellate parasite infecting humans, wild and domestic mammals in Central and Latin America. The share of genotypic, phenotypic, and biological similarities with the virulent, human-infective T. cruzi and T. brucei, allows comparative studies on mechanisms of pathogenesis. In this study, investigation of the T. rangeli Arginine Kinase (TrAK) revealed two highly similar copies of the AK gene in this taxon, and a distinct expression profile and activity between replicative and infective forms. Although TrAK expression seems stable during epimastigotes growth, the enzymatic activity increases during the exponential growth phase and decreases from the stationary phase onwards. No differences were observed in activity or expression levels of TrAK during in vitro differentiation from epimastigotes to infective forms, and no detectable AK expression was observed for blood trypomastigotes. Overexpression of TrAK by T. rangeli showed no effects on the in vitro growth pattern, differentiation to infective forms, or infectivity to mice and triatomines. Although differences in TrAK expression and activity were observed among T. rangeli strains from distinct genetic lineages, our results indicate an up-regulation during parasite replication and putative post-translational myristoylation of this enzyme. We conclude that up-regulation of TrAK activity in epimastigotes appears to improve proliferation fitness, while reduced TrAK expression in blood trypomastigotes may be related to short-term and subpatent parasitemia in mammalian hosts.

Keywords: ATP homeostasis; Arginine kinase; Energetic demand; Stage-regulated activity; Trypanosoma rangeli.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arginine Kinase / biosynthesis
  • Arginine Kinase / classification
  • Arginine Kinase / genetics
  • Arginine Kinase / metabolism*
  • Blotting, Western
  • DNA, Protozoan / isolation & purification
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Flagella / enzymology
  • Fluorescent Antibody Technique, Indirect
  • Mice
  • Mice, Inbred BALB C
  • Phylogeny
  • Protein Processing, Post-Translational*
  • Sequence Alignment
  • Trypanosoma cruzi / classification
  • Trypanosoma cruzi / enzymology*
  • Trypanosoma cruzi / genetics
  • Trypanosoma cruzi / pathogenicity
  • Trypanosoma rangeli / classification
  • Trypanosoma rangeli / enzymology*
  • Trypanosoma rangeli / genetics
  • Trypanosoma rangeli / pathogenicity
  • Up-Regulation
  • Virulence

Substances

  • DNA, Protozoan
  • Arginine Kinase