A link between mitochondrial gene expression and life stage morphologies in Trypanosoma cruzi

Abstract

The protozoan Trypanosoma cruzi has a complicated dual-host life cycle, and starvation can trigger transition from the replicating insect stage to the mammalianinfectious nonreplicating insect stage (epimastigote to trypomastigote differentiation). Abundance of some mature RNAs derived from its mitochondrial genome increase during culture starvation of T. cruzi for unknown reasons. Here, we examine T. cruzi mitochondrial gene expression in the mammalian intracellular replicating life stage (amastigote), and uncover implications of starvation-induced changes in gene expression. Mitochondrial RNA levels in general were found to be lowest in actively replicating amastigotes. We discovered that mitochondrial respiration decreases during starvation in insect stage cells, despite the previously observed increases in mitochondrial mRNAs encoding electron transport chain (ETC) components. Surprisingly, T. cruzi epimastigotes in replete medium grow at normal rates when we genetically compromised their ability to perform insertion/deletion editing and thereby generate mature forms of some mitochondrial mRNAs. However, these cells, when starved, were impeded in the epimastigote to trypomastigote transition. Further, they experience a short-flagella phenotype that may also be linked to differentiation. We hypothesize a scenario where levels of mature RNA species or editing in the single T. cruzi mitochondrion are linked to differentiation by a yet-unknown signaling mechanism. K E Y W O R D S gene expression, life cycle stages, organelles, ribonuclease, RNA editing, trypanosomiasis S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Ramirez-Barrios R, Susa EK, Smoniewski CM, Faacks SP, Liggett CK, Zimmer SL. A link between mitochondrial gene expression and life stage morphologies in Trypanosoma cruzi. Mol Microbiol.

Kinetic Characterization and Inhibition of Trypanosoma cruzi Hypoxanthine–Guanine Phosphoribosyltransferases

“…Apart from the social, economic, and political factors that diminish the research and development of novel drugs for the treatment of all neglected tropical diseases, 11 , 12 the intrinsic complexities of the life cycle of CD’s etiological agent— Trypanosoma cruzi 13 − 18 —exacerbate the challenges in developing specific and selective therapies against this important disease. T. cruzi known genetic plasticity and variable gene expression along its life cycle 8 , 19 is linked to its ability to evade the host’s immune system. 20 − 23 …”

“…T. cruzi known genetic plasticity and variable gene expression along its life cycle 8,19 is linked to its ability to evade the host's immune system. 20−23 T. cruzi, like other parasitic protozoa, is an obligatory purine auxotroph that lacks a functional de novo synthetic pathway to make purine nucleotides.…”

“…The HGPRTs are thus promising drug targets because of their central importance in nucleotide biosynthesis in T. cruzi. 27−30 Noteworthy, a previous study showed that 19 T. cruzi strains susceptible to benznidazole and nifurtimox treatment in vivo were polymorphic for HGPRT, 27 indicating a direct correlation between T. cruzi HGPRT polymorphism and drug susceptibility. The expression of HGPRTs along the life cycle of the closely related organism Trypanosoma brucei indicates its presence in both human and insect host stages, 31 as expected for their essential roles in purine base incorporation, thus supporting its value as a viable drug target.…”

“…T. cruzi known genetic plasticity and variable gene expression along its life cycle , is linked to its ability to evade the host’s immune system. − …”

Propriedades biológicas da proteína miosina-1 e do receptor dectina-1 na infecção in vitro por Trypanosoma cruzi

“…As formas não replicativas e infectantes incluem os tripomastigotas metacíclicos -encontrados nas fezes e urina do inseto vetor; e os tripomastigotas circulantesobservado no sangue periférico de mamíferos. Portanto, o T. cruzi consegue além de sobreviver, se multiplicar dentro das células hospedeiras de mamíferos (BATISTA et al, 2020;RAMIREZ-BARRIOS et al, No sangue periférico dos hospedeiros mamíferos estão os tripomastigotas de T. cruzi e consequentemente, o inseto triatomíneo ingere essas formas durante o repasto sanguíneo (ANDREWS et al, 1987;LEY et al, 1988). Os parasitas passam para o intestino do vetor e os tripomastigotas sofrem diferenciação, no ambiente do intestino médio e transformam-se em epimastigotas, que são formas replicativas (TYLER; ENGMAN, 2001).…”