Publication:
Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi.

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2021-04-08

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Ibarrola-Vannucci, Ana K
De Pablos, Luis M
Retana-Moreira, Lissette
Cornet-Gomez, Alberto
Cruz-Bustos, Teresa
Schijman, Alejandro G
Ramírez, José L
Vílchez, Susana
Osuna, Antonio

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Chagas disease is the third most important neglected tropical disease. There is no vaccine available, and only two drugs are generally prescribed for the treatment, both of which with a wide range of side effects. Our study of T. cruzi PHBs revealed a pleiotropic function in different stages of the parasite, participating actively in the transformation of the non-infective replicative epimastigote form into metacyclic trypomastigotes and also in the multiplication of intracellular amastigotes. To obtain and confirm our results, we applied several tools and techniques such as electron microscopy, immuno-electron microscopy, bioinformatics analysis and molecular biology. We transfected T. cruzi clones with the PHB genes, in order to overexpress the proteins and performed a CRISPR/Cas9 disruption to obtain partially silenced PHB1 parasites or completely silenced PHB2 parasites. The function of these proteins was also studied in the biology of the parasite, specifically in the transformation rate from non-infective forms to the metacyclic infective forms, and in their capacity of intracellular multiplication. This research expands our understanding of the functions of PHBs in the life cycle of the parasite. It also highlights the protective role of prohibitins against ROS and reveals that the absence of PHB2 has a lethal effect on the parasite, a fact that could support the consideration of this protein as a possible target for therapeutic action.

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MeSH Terms

Animals
Chagas Disease
Clustered Regularly Interspaced Short Palindromic Repeats
Computer Simulation
Life Cycle Stages
Male
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Prohibitins
Protozoan Proteins
Rats
Rats, Wistar
Repressor Proteins
Trypanosoma cruzi

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