Modulation of Virulence Factors during Trypanosoma cruzi Differentiation

Abstract

Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. This protozoan developed several mechanisms to infect, propagate, and survive in different hosts. The specific expression of proteins is responsible for morphological and metabolic changes in different parasite stages along the parasite life cycle. The virulence strategies at the cellular and molecular levels consist of molecules responsible for mediating resistance mechanisms to oxidative damage, cellular invasion, and immune evasion, performed mainly by surface proteins. Since parasite surface coat remodeling is crucial to invasion and infectivity, surface proteins are essential virulence elements. Understanding the factors involved in these processes improves the knowledge of parasite pathogenesis. Genome sequencing has opened the door to high-throughput technologies, allowing us to obtain a deeper understanding of gene reprogramming along the parasite life cycle and identify critical molecules for survival. This review therefore focuses on proteins regulated during differentiation into infective forms considered virulence factors and addresses the current known mechanisms acting in the modulation of gene expression, emphasizing mRNA signals, regulatory factors, and protein complexes.

Transcriptomic analysis of N-terminal mutatedTrypanosoma cruziUBP1 knockdown underlines the importance of this RNA-binding protein in parasite development

“…TcUBP1 functions by stabilizing or destabilizing myriad mRNAs, depending on the interaction with other stage-specific components of ribonucleoprotein complexes throughout the parasite life cycle [10]. Our previous findings revealed that overexpression of TcUBP1 in insect-dwelling epimastigotes enhanced the abundance of TcS transcripts and altered their subcellular localization to a perinuclear region [36, 44]. These observations were further supported by a shift toward mRNA expression characteristic of infective trypomastigotes [16, 36].…”

A versatile 2A peptide-based strategy for ectopic expression and endogenous gene tagging in Trypanosoma cruzi

“…Genetic manipulation of T. cruzi is most frequently performed in the epimastigote replicative stage. Therefore, the inclusion of histone H4 intergenic sequence allows to target, for endogenous tagging, any gene of interest even those that are not physiologically expressed in the insect form such as several mammalian host-associated virulence factors [ [46] , [47] , [48] ].…”

Transcriptomic analysis of N-terminal mutated Trypanosoma cruzi UBP1 knockdown underlines the importance of this RNA-binding protein in parasite development

“…TcUBP1 functions by stabilizing or destabilizing myriad mRNAs, depending on the interaction with other stage-specific components of ribonucleoprotein complexes throughout the parasite life cycle [ 10 ]. Our previous findings revealed that overexpression of TcUBP1 in insect-dwelling epimastigotes enhanced the abundance of TcS transcripts and altered their subcellular localization to a perinuclear region [ 36 , 46 ]. These observations were further supported by a shift toward mRNA expression characteristic of infective trypomastigotes [ 16 , 36 ].…”